GESIDA/PETHEMA recommendations on the diagnosis and treatment of lymphomas in patients infected by the human immunodeficiency virus

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"aff0005" ] ] ] 6 => array:3 [ "nombre" => "José Luis" "apellidos" => "Díez-Martín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "Salvador" "apellidos" => "Villà" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 8 => array:3 [ "nombre" => "Rafael" "apellidos" => "Rubio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 9 => array:3 [ "nombre" => "Javier" "apellidos" => "Menárguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 10 => array:3 [ "nombre" => "José-María" "apellidos" => "Ribera Santasusana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Institut Català d’Oncologia, Hospital Universitari Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autónoma de Barcelona, Badalona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital La Fe, Valencia, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Hospital 12 de Octubre, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recomendaciones de GESIDA/PETHEMA sobre el diagnóstico y tratamiento de los linfomas en pacientes infectados por el virus de la inmunodeficiencia humana" ] ] "textoCompleto" => "IntroductionLymphomas associated with HIV infection are grouped into three entities: systemic non-Hodgkin's lymphomas (NHL), primary central nervous system lymphoma (PCNSL), and Hodgkin's lymphoma (HL). Systemic NHL associated with HIV infection are more often B-cell lymphomas of great malignancy and some rare histological types that occur almost exclusively in this group of patients. PCNSL is a variety of NHL limited to the craniospinal axis that appears in patients with profound immunodeficiency. Both PCNSL and systemic NHL are considered AIDS-defining diseases. However, HL was not previously included as an AIDS-defining disease by the Centers for Disease Control and Prevention (CDC)<a class="elsevierStyleCrossRef" href="#bib0935">1</a> even though its incidence among people infected with HIV is much higher than that observed in the general population.The introduction of combination antiretroviral therapy (cART) in 1996 radically changed the natural history of HIV infection and drastically reduced the incidence of tumours such as PCNSL, which occur with very low CD4+ T lymphocyte counts.<a class="elsevierStyleCrossRef" href="#bib0940">2</a> After the introduction of cART, lymphomas that usually occur with higher CD4+ T lymphocyte counts, such as Burkitt's lymphoma (BL) and HL also decreased, but not as significantly.<a class="elsevierStyleCrossRefs" href="#bib0945">3,4</a> In addition, the use of cART has been decisive in the improvement of the prognosis of these tumours.<a class="elsevierStyleCrossRefs" href="#bib0940">2,5–8</a>This document updates the recommendations on the diagnosis and treatment of lymphomas in HIV-infected patients published in 2008 by a panel of experts from the AIDS Study Group (GESIDA) and the Spanish Program for Haematology Treatments PETHEMA.<a class="elsevierStyleCrossRef" href="#bib0975">9</a> As in the previous edition, these recommendations are accompanied by a categorization of the level of scientific evidence following the classification scheme for clinical practice of the United States Public Health Service and the Infectious Diseases Society of America (USPHS/IDSA) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Systemic non-Hodgkin's lymphomasHistopathology and classificationThe variety or histological subtype is the most important variable to predict clinical behaviour and to establish the prognosis of lymphomas. The WHO classification continues to be the accepted standard for terminology and classification of lymphoid neoplasms. Some changes were introduced in the latest edition of this classification, which is an update of the one published in 2008, including the subdivision of diffuse large B-cell lymphomas (DLBCL) depending on its germinal centre or non-germinal centre origin<a class="elsevierStyleCrossRef" href="#bib0980">10</a> (<a class="elsevierStyleCrossRef" href="#sec0310">Appendix 1</a>).NHL associated with HIV infection are mainly of B-lineage, in particular DLBCL (73%) and less frequently BL (19%).<a class="elsevierStyleCrossRef" href="#bib0955">5</a> There are rare varieties but strongly linked to HIV infection, such as plasmablastic lymphoma and other related to type 8 human herpes virus (HHV-8), such as primary effusion lymphoma and multicentric Castleman's disease (MCD).Diagnosis and extension studySystemic NHL associated with HIV infection usually occur in young men with CD4+ lymphocyte values <200/mm3, frequently being an AIDS-defining disease. The tumour is usually in advanced stages and is often accompanied by B symptoms and extranodal involvement, particularly of the bone marrow. There may also be central nervous system (CNS) involvement, both at the onset and during the course of the disease. The leptomeningeal involvement predominates in the initial stages, occurs more frequently when there is bone marrow or otorhinolaryngological area invasion and may be asymptomatic. The involvement of the brain parenchyma in the form of masses is more common in the context of a progressive and refractory lymphoma.The diagnosis of lymphoma and the identification of the specific subtype require a histological study with immunohistochemistry and sometimes cytogenetic and molecular studies. It is recommended to study the complete lymph node or a large sample of infiltrated tissue. Samples obtained by fine needle aspiration are never enough to establish the correct diagnosis. However, in some cases, a needle biopsy may be used when it is not possible to obtain lymphadenopathy or tissue sample by biopsy.Once the diagnosis is confirmed, an extension study should be done<a class="elsevierStyleCrossRefs" href="#bib0985">11,12</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). In patients who are going to receive treatment with anthracyclines, it is also recommended to determine the ejection fraction of the left ventricle using echocardiography or isotopic ventriculography, both at baseline and during progression.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>There is no specific staging system for NHLs, but the Ann Arbor/Cotswolds staging system has traditionally been used,<a class="elsevierStyleCrossRefs" href="#bib0995">13,14</a> which was designed for HL (<a class="elsevierStyleCrossRef" href="#sec0315">Appendix 2</a>). A new, more specific system for NHLs (the Lugano classification) derived from the Ann Arbor/Cotswolds classification has recently been proposed<a class="elsevierStyleCrossRef" href="#bib0990">12</a> (<a class="elsevierStyleCrossRef" href="#sec0320">Appendix 3</a>).Factors related to the prognosisIn patients with HIV infection and NHL and before the introduction of cART, factors related to the prognosis were mainly related to the characteristics of the patients and the viral infection itself, and to a lesser extent to factors associated with NHL.<a class="elsevierStyleCrossRefs" href="#bib1005">15–18</a> However, after the introduction of cART, the variables associated with HIV lost prognostic importance and the factors of NHL became more important.<a class="elsevierStyleCrossRefs" href="#bib0955">5,17,19,20</a>Factors related to the prognosis for aggressive adult NHL are very well known since the publication of the predictive model of the international prognostic index,<a class="elsevierStyleCrossRef" href="#bib1035">21</a> better known by its acronym IPI (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). According to the criteria of this system, patients are classified into low, low intermediate, high intermediate and high-risk groups. Age-adjusted IPI is a simplified model for younger populations that classifies patients according to age (≤60 or >60years), stage, general condition and serum LDH.<a class="elsevierStyleCrossRef" href="#bib1035">21</a> Both the IPI and the age-adjusted IPI have shown prognostic value in patients with HIV infection and NHL.<a class="elsevierStyleCrossRefs" href="#bib0955">5,17–20</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>TreatmentDiffuse large B-cell lymphomaIn patients without HIV infection, DLBCL is a potentially curable disease whose treatment depends on the stage of the tumour. For localized stages, chemotherapy combined with immunotherapy targeting the CD20 antigen and radiotherapy of the affected area is used. Advanced stages are treated with the combination of chemotherapy and immunotherapy. The adequate control of HIV infection with cART and the use of hematopoietic growth factors have made it possible for patients with HIV and lymphoma to receive the same chemotherapy regimens as patients without HIV infection, with comparable clinical results.<a class="elsevierStyleCrossRefs" href="#bib1040">22–24</a>The most commonly used first-line polychemotherapy regimen for DLBCL is CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) with anti-CD20 (R-CHOP), with whom complete remission (CR) is obtained in 60–80% of patients with NHL in stages II to IV. There are few data showing that 8 cycles are more effective than 6, therefore, 6 cycles are usually administered with a 21 day interval between each one. It is very important to administer the appropriate doses of cytostatics and to adjust to the intervals, since the reductions in drug-dose intensity, particularly adriamycin and cyclophosphamide, decrease the percentage of CR.In patients with HIV infection, two phase II studies have been published with R-CHOP in which the percentages of CRs were 69 and 77%, with an overall survival (OS) at 2 and 3 years of 75 and 56%, respectively.<a class="elsevierStyleCrossRefs" href="#bib1055">25,26</a> Although some studies have shown better results with infusion regimens such as R-EPOCH compared to historical controls treated with R-CHOP,<a class="elsevierStyleCrossRefs" href="#bib1065">27–29</a> no regimen has surpassed R-CHOP in randomized clinical trials, so the latter is considered the standard regimen in our environment.<a class="elsevierStyleCrossRef" href="#bib1080">30</a>In patients with HIV infection and NHL, the addition of rituximab to chemotherapy is safe and recommendable, although there is some hesitation in highly-immunocompromised patients due to the results of a phase III clinical trial published in 2005, where R-CHOP was compared to CHOP, in which mortality was higher due to infection in the R-CHOP arm in patients with CD4+ T lymphocyte values <50/mm3.<a class="elsevierStyleCrossRef" href="#bib1085">31</a>Treatment with radiotherapy in patients with lymphoma associated with HIV infection does not differ substantially from that indicated in the general population,<a class="elsevierStyleCrossRef" href="#bib1090">32</a> and as such it plays a secondary role in the treatment of NHL, having a more decisive role in the treatment of HL (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). Adjuvant radiotherapy on the affected area in patients with NHL in localized stages (IA and IIA) is indicated after completing 3 cycles of chemotherapy. In bulky mass lymphomas, radiation therapy can be administered to the mass after chemotherapy is complete. Treatment with radiotherapy can also be used for palliative purposes in cases of uncontrolled pain, compression of adjacent structures, spinal cord compression, bleeding or lack of chemotherapy effectiveness.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Aggressive B-cell lymphoma with MYC and BCL2 and/or BCL6 gene rearrangementIn 5–10% of the DLBCL there is a rearrangement of the gene MYC, which is often associated with translocations of the gene BCL2 and/or the BCL6. These NHL are considered as a separate category in the new WHO classification due to their extraordinary aggressiveness, poor response to standard treatments and poor prognosis.<a class="elsevierStyleCrossRefs" href="#bib0980">10,33,34</a> They have also been called double hit (DH) or triple hit (TH), according to the presence of two or three translocations. What the best treatment for DH or TH NHL is still unknown, but it is known that their response is worse in the case of R-CHOP than DLBCL, with CR percentages of 40%, OS at 2 years of 35–41% and OS at 5 years of 25–30%.<a class="elsevierStyleCrossRefs" href="#bib1105">35–37</a> The intensive chemotherapy regimens used to treat BL have been used with these lymphomas, with slightly better outcomes than those obtained with R-CHOP.<a class="elsevierStyleCrossRefs" href="#bib1120">38,39</a> The AD-EPOCH-R regimen (dose-adjusted EPOCH-rituximab) has shown promising results and could be used in HIV-infected patients with this type of lymphoma.<a class="elsevierStyleCrossRefs" href="#bib1120">38,40,41</a>Burkitt's lymphomaThis lymphoma is characterized by the deregulation of the MYC oncogene and for its great aggressiveness. In patients with HIV infection, BL usually occurs in patients without previous diagnosis of AIDS and with a relatively preserved immune system. Despite this, the regimens used for the DLBCL have had very poor results in the BL, as it happens in the population not infected with HIV.The best results against BL have been obtained with multidrug chemotherapy regimens with cytostatics without cross resistance and good penetration in the CNS together with intrathecal prophylaxis. In fact, in patients with BL without HIV infection, the cyclophosphamide, adriamycin, vincristine and methotrexate regimen (CODOX-M) alternating with ifosfamide, etoposide and cytarabine (IVAC) has achieved CR in 90% of patients with event-free survival (EFS) at 2 years in 50–70% of cases.<a class="elsevierStyleCrossRefs" href="#bib1140">42–44</a> Good therapeutic results have also been obtained in BL with hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (Hyper-CVAD).<a class="elsevierStyleCrossRef" href="#bib1155">45</a> Experience with Hyper-CVAD and CODOX-M/IVAC for the treatment of BL in patients with HIV is not extensive, but published studies show a CR in 64–92% of cases, survival at 2 years from 47 to 59% and a toxicity similar to that of patients without HIV infection.<a class="elsevierStyleCrossRefs" href="#bib1160">46–49</a>Some clinical trials in patients without HIV infection indicate that the addition of rituximab to these intensive chemotherapy regimens improves efficacy without significantly increasing toxicity.<a class="elsevierStyleCrossRefs" href="#bib1180">50,51</a> Also in patients with HIV infection and BL, intensive chemotherapy regimens with rituximab have been studied, such as the B-ALL/NHL2002 protocol of the German multicentre adult acute lymphoblastic leukaemia (GMALL) study group and its Spanish variant Burkimab, with which CR has been achieved in more than 80% of cases, with an 11% mortality in induction and a higher incidence of infections than in HIV negative patients treated with the same protocol.<a class="elsevierStyleCrossRefs" href="#bib1190">52,53</a> On the other hand, in the AIDS Malignancy Consortium 048 trial, the addition of rituximab to the modified CODOX-M/IVAC regimen has achieved a first-year OS of 72% with a toxicity similar to that of individuals without HIV infection.<a class="elsevierStyleCrossRef" href="#bib1200">54</a> The R-EPOCH regimen has also been evaluated in BL in a prospective study with 30 patients without CNS involvement, 11 of whom were infected with HIV<a class="elsevierStyleCrossRef" href="#bib1205">55</a>; after a median follow-up of 73 months 100% of the patients were alive and 90% free of progression.It is important to note that patients with BL should be treated by teams with experience in the management of this type of lymphomas.Plasmablastic lymphomaPlasmablastic lymphoma is a very aggressive and infrequent lymphoma that is considered a different entity from the DLBCL and that mainly affects HIV-infected population.<a class="elsevierStyleCrossRef" href="#bib1210">56</a> Initially, cases with involvement of the oral cavity were described,<a class="elsevierStyleCrossRef" href="#bib1215">57</a> but its appearance has been later described in other locations.<a class="elsevierStyleCrossRef" href="#bib1220">58</a> The prognosis, even in the era of cART, is very poor, with a median survival of less than one year.<a class="elsevierStyleCrossRef" href="#bib1220">58</a> Intensive chemotherapy regimens have not shown better results than CHOP, so there is currently no standard treatment for this type of NHL. If the patient's condition permits, a consolidation with an autologous hematopoietic stem cell transplant (HSCT) is generally recommended, as well as intrathecal prophylaxis.Recently, drugs used for the treatment of multiple myeloma have been studied, given the plasmocytic differentiation of plasmablastic lymphoma. The most used has been bortezomib, a proteasome inhibitor that has been used alone or in combination with chemotherapy, both as a salvage therapy and as a first-line treatment.<a class="elsevierStyleCrossRefs" href="#bib1225">59,60</a> Recently, the outcome of the plasmablastic lymphoma treatment with bortezomib and EPOCH in 3 patients have been reported, all of whom achieved CR with survival between 12 and 24 months at the time of publication.<a class="elsevierStyleCrossRef" href="#bib1235">61</a>Primary effusion lymphomaPrimary effusion lymphoma is an uncommon variety of NHL associated with HIV infection that frequently occurs along with Kaposi's sarcoma (KS). HHV-8 plays a key role in the pathogenesis of both tumour,<a class="elsevierStyleCrossRef" href="#bib1240">62</a> DNA virus that infects mainly lymphoblastic cells, producing a state of latent infection. Primary effusion lymphoma typically originates in some of the serous cavities such as pleura, pericardium or peritoneum, so that the clinical manifestations depend on the cavity in which the tumour originates. Tumour masses are rarely developed, although lymphoma can spread through serosa surfaces.<a class="elsevierStyleCrossRef" href="#bib1240">62</a>The diagnosis is made by cytological fluid examination. The key diagnostic criterion for primary effusion lymphoma is the presence of HHV-8 in the nuclei of the malignant cells, which is demonstrated by positive immunohistochemical staining for the nuclear antigen 1 associated with latency (LANA-1). Despite the frequent co-infection with EBV, the latency membrane protein (LMP1) staining is negative. The general lymphoma staging system (IPI) is not useful for primary effusion lymphoma, which, by definition, is in stage IV. However, an extension study is recommended through Positron Emission Tomography (PET) – Thoracic, abdominal and pelvic computed tomography (CT). It is often necessary to perform cardiac ultrasound, bone marrow biopsy or lumbar puncture within the initial extension study. In a series with 28 cases, the absence of cART at the time of diagnosis and the poor general state of the patient were identified as the main factors of poor prognosis.<a class="elsevierStyleCrossRef" href="#bib1245">63</a>There is no standardized treatment for primary effusion lymphoma. Isolated cases have been described in which CR with CHOP and cART was achieved.<a class="elsevierStyleCrossRefs" href="#bib1250">64,65</a> However, in a single-centre series with 11 cases treated with CHOP and cART, CR was obtained in 42%, with a median survival of 6 months.<a class="elsevierStyleCrossRef" href="#bib1260">66</a> There is very little experience with EPOCH<a class="elsevierStyleCrossRef" href="#bib1265">67</a> and also with autologous HSCT<a class="elsevierStyleCrossRefs" href="#bib1270">68,69</a> or allogeneic HSCT,<a class="elsevierStyleCrossRef" href="#bib1280">70</a> with results still inconclusive. However, given the poor prognosis of this tumour, HSCT is a therapeutic option that should be considered in appropriately selected patients. Bortezomib has in vitro activity against primary effusion lymphoma<a class="elsevierStyleCrossRef" href="#bib1285">71</a> and a phase II clinical trial is currently underway of bortezomib associated with chemotherapy for the treatment of this lymphoma.Multicentric Castleman's diseaseMCD is an aggressive lymphoproliferative process that occurs more frequently in HIV-infected patients than in the general population. Although not considered a lymphoma, patients with MCD, especially those infected with HIV, are at risk of progression to NHL.<a class="elsevierStyleCrossRef" href="#bib1290">72</a> There are two histological variants of MCD: the hyalinovascular and the plasmocellular. The latter is the one usually present in HIV-infected patients. In these patients, the incidence of MCD has increased since the introduction of cART and an association with CD4+ T lymphocyte values or with the administration of cART has not been demonstrated.<a class="elsevierStyleCrossRef" href="#bib1295">73</a> The etiopathogenesis of this entity is not well known, but the available information indicates that HHV-8 plays a key role, since high levels of HHV-8 DNA have been found in peripheral blood mononuclear cells as well as in the plasma of MCD patients.<a class="elsevierStyleCrossRefs" href="#bib1300">74,75</a>MCD typically presents with fever, sweating and constitutional symptoms. On physical examination, there are usually enlarged lymph nodes and sometimes hepatomegaly and/or splenomegaly. In addition, the coexistence of KS is common in patients with HIV infection and MCD.There are hardly any therapeutic clinical trials on MCD and most of the information in this regard comes from clinical cases or series with few patients. In the MCD associated with HIV, treatment with rituximab has achieved remissions in 67–71% of patients, with survival at 2 years of 90–95%.<a class="elsevierStyleCrossRefs" href="#bib1310">76,77</a> It is important to note that in patients with HIV infection and MCD, treatment with rituximab has been associated with a reduction in the risk of developing NHL,<a class="elsevierStyleCrossRef" href="#bib1320">78</a> although it may favour the occurrence of KS. The usual regimen consists of 4 375mg/m2 doses of rituximab at one-week intervals. However, in severe cases, the combination of rituximab with chemotherapy such as CHOP or etoposide should be considered (100mg/m2×4 weeks).<a class="elsevierStyleCrossRefs" href="#bib1090">32,79</a> Given that the symptomatology of the MCD seems to be related to high plasma levels of interleukin-6 (IL-6), monoclonal antibodies against this cytokine (siltuximab) or its receptor (tocilizumab) have been used, which has been effective in HIV-negative patients.<a class="elsevierStyleCrossRefs" href="#bib1330">80,81</a> However, the experience in HIV-positive patients is very limited. HHV-8 is sensitive in vitro to different antivirals such as ganciclovir, foscarnet and cidofovir,<a class="elsevierStyleCrossRef" href="#bib1340">82</a> and series with few HIV-infected and MCD patients have been published in which treatment with ganciclovir<a class="elsevierStyleCrossRef" href="#bib1345">83</a> or valganciclovir<a class="elsevierStyleCrossRef" href="#bib1350">84</a> has been associated with decreased HHV-8 viraemia and clinical improvement.Lymphomatous meningitisThe prevalence of CNS involvement in HIV-associated NHL at the time of diagnosis is 5–15% and the typical form is lymphomatous meningitis (LM). In the population in question, as in patients without HIV infection, the frequency of LM varies according to the type of NHL and is more common in the BL (25–30%) than in DLBCL (5–10%).<a class="elsevierStyleCrossRefs" href="#bib1355">85,86</a> In one study, the frequency of secondary CNS involvement was lower in patients receiving cART before NHL than in patients not receiving cART.<a class="elsevierStyleCrossRef" href="#bib1365">87</a>DiagnosisLM may occur without clinical data of neurological involvement, and for this reason a cerebrospinal fluid (CSF) evaluation should be part of the extension study of aggressive NHL associated with HIV. The study should include glucose and protein quantification, as well as a cellularity study by light microscopy after CSF cytocentrifugation, and by flow cytometry. When these techniques are not conclusive, the study of the rearrangement of the immunoglobulin heavy-chain gene in the CSF may be useful. In one study, the presence of EBV DNA in CSF was associated with an increased risk of CNS involvement by NHL at the time of diagnosis or relapse.<a class="elsevierStyleCrossRef" href="#bib1370">88</a> Patients with clinical manifestations suggestive of LM should undergo imaging tests, preferably magnetic resonance imaging (MRI) with contrast.Central nervous system prophylaxisThere are no studies that have evaluated the efficacy and safety of meningeal prophylaxis in patients with NHL and HIV infection. Despite this, this committee considers that it should be carried out in patients with “high risk” NHL, such as BL, lymphomas with MYC gene rearrangement, plasmablastic lymphoma and DLBCL with elevated LDH and more than one extranodal site or with invasion of the epidural space, breast, kidney, testicle or bone marrow (AII).<a class="elsevierStyleCrossRefs" href="#bib1375">89–91</a> There are several prophylaxis regimens, but this consensus group recommends intrathecal (IT) administration of methotrexate (MTX) (12mg), cytosine arabinoside (Ara-C) (30mg) and hydrocortisone (20mg) on day 1 of each cycle (BII). An alternative to IT prophylaxis is the use of high doses of systemic chemotherapy, usually intravenous MTX with or without IT chemotherapy (CIII). The available information suggests that in order to achieve adequate levels of MTX in the CSF and brain parenchyma, doses of the drug should be administered intravenously 3g/m2.<a class="elsevierStyleCrossRef" href="#bib1390">92</a> High doses of intravenous MTX can be administered concurrently with regimens such as R-CHOP or R-CHOP with etoposide (R-CHOEP).<a class="elsevierStyleCrossRefs" href="#bib1395">93,94</a> In patients with HIV infection, administration of high doses of intravenous MTX with R-CHOP could cause delays in subsequent cycles of R-CHOP due to the greater tendency of these patients to suffer from cytopenia with chemotherapy, which could result counterproductive in terms of good systemic disease control.TreatmentFor the treatment of LM, triple IT therapy with MTX (12mg), Ara-C (30mg) and hydrocortisone (20mg) every 3 or 4 days until the disappearance of tumour cells in CSF and then 2 more doses, administering at least 5 doses (BII).Ara-C in liposomal depot form has a longer half-life and better CNS distribution than conventional Ara-C. It can be administered biweekly, which avoids repeated lumbar punctures and, in some cases, the placement of Ommaya-type reservoirs. The recommended regimen contemplates an induction phase with 50mg biweekly until completing 5 doses, followed by a consolidation and maintenance phase of 50mg once a month until completing 5 doses (BII). In a study with patients without HIV infection, treatment of LM with liposomal Ara-C was more effective than conventional Ara-C treatment and was associated with better quality of life.<a class="elsevierStyleCrossRef" href="#bib1405">95</a> There is less information in HIV-infected patients, although the experience in a small series was favourable.<a class="elsevierStyleCrossRef" href="#bib1410">96</a> The administration of liposomal IT Ara-C can associate neurological toxicity when administered concomitantly with MTX at high doses and Ara-C systemically.<a class="elsevierStyleCrossRef" href="#bib1415">97</a> For this reason, it is recommended to administer dexamethasone by IT route with each liposomal Ara-C dose and separate its administration from other intravenous cytostatics that cross the blood-brain barrier well by at least 7 days, mainly Ara-C.Craniospinal radiation therapy is currently not recommended for prophylaxis or treatment of CNS involvement in patients with systemic NHL. First, because there is an effective alternative such as intrathecal and/or systemic chemotherapy. Secondly, because it produces great toxicity, both haematological and non-haematological. Finally, because it is technically complex given that there is a risk of overlapping irradiation volumes on various anatomical regions.Practical recommendations for the treatment of systemic lymphomas in HIV-infected patientsThe overview of the treatment of systemic NHL associated with HIV infection is detailed in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>Diffuse large B-cell lymphoma6 cycles of R-CHOP administered every 21 days are recommended (AII), keeping in mind that patients with CD4+ T lymphocytes <50/mm3 could have more infectious complications. The R-EPOCH-DA infusion regimen may be an alternative, although it has not been shown to be more effective than R-CHOP and is more toxic than the latter (BII). In patients with stage IA or IIA the recommended treatment is 3 cycles of R-CHOP administered every 21 days followed by radiotherapy over affected area (AIII).Burkitt's lymphomaPatients with good immunological status and good general condition should receive intensive chemotherapy with regimens such as CODOX-M/IVAC, Hyper-CVAD or a similar protocol as that of the PETHEMA group (Burkimab) designed specifically for this tumour (AII). In addition, it is recommended to associate rituximab with the chemotherapy regimens (AI). These intensive regimens should be used by experienced teams, since they carry a toxicity mortality of 7–10%. Other regimens can be used in patients with significant comorbidity, such as EPOCH (CII).Aggressive B-cell lymphoma with MYC and BCL2 and/or BCL6 gene rearrangementGiven the poor results obtained with the R-CHOP regimen, intensive chemotherapy regimens designed for BL (BII) or the AD-EPOCH-R regimen, which has shown promising results (BII), can be used.Plasmablastic lymphomaThere is no good therapeutic option at present for this lymphoma. Intensive regimens such as DA-EPOCH, which have shown greater efficacy than CHOP in few patient series and isolated cases (BII), can be considered. Chemotherapy such as EPOCH can also be used together with bortezomib, although the available data are limited (BIII). Autologous HSCT could be considered in patients with rearranged MYC in those that have not reached a complete response (CIII).Multicentric Castleman's diseaseIt is recommended to administer rituximab. The usual pattern is 4 doses of 375mg/m2 at 1-week intervals (AII). In the most severe cases, the combination of rituximab with CHOP or etoposide at a dose of 100mg/m2 should be considered (BII).Primary effusion lymphomaThere is no standardized treatment for primary effusion lymphoma. The first-line treatment can be performed with CHOP or EPOCH. Comparative studies have not been carried out and there is no standard optimal therapy (AII). Given the poor prognosis of this tumour, autologous HSCT is a therapeutic option that should be considered in appropriately selected patients (CIII). Another therapeutic option not yet consolidated is bortezomib associated with chemotherapy (DIII).Second-line treatmentsThere is little information about second-line treatments in HIV-infected patients. It is important to differentiate the treatment of relapsed NHL from the treatment of refractory NHL.Relapsed systemic lymphomaRelapses of systemic NHL in HIV-infected patients are a relatively common problem. A relapse was documented in 16% of patients who achieved CR in the collaborative study of GESIDA and PETHEMA of NHL during the era of cART. The relapse occurred a median of 10 months after CR with an interquartile range from 2 to 16 months.<a class="elsevierStyleCrossRef" href="#bib0955">5</a> Some patients in first relapse achieve a second CR after a second-line treatment. When choosing a second-line treatment, three aspects should be assessed: the quality of life of the patient (general condition and associated diseases), the previous treatments and the bone marrow reserve. In patients with a good general condition and with HIV infection under control, who have previously received R-CHOP or R-EPOCH, treatment with etoposide, cisplatin, methylprednisolone and cytarabine (ESHAP), generally combined with rituximab, may be considered.<a class="elsevierStyleCrossRef" href="#bib1420">98</a> In those in which CR or a good partial remission of NHL is achieved after second-line chemotherapy, consolidation with autologous HSCT can be considered. Several patient and case–control series studies have shown that the results of autologous HSCT are not different from those observed in the non-immunocompromised population.<a class="elsevierStyleCrossRefs" href="#bib1425">99,100</a> The results with the different treatments offer CR rates around 30%, although survival at one year in patients who achieve CR is around 80%, with or without autologous HSCT.<a class="elsevierStyleCrossRef" href="#bib1435">101</a> In patients with poor general condition, palliative chemotherapy should be administered with acceptable toxicity profile protocols.Systemic lymphoma refractory to chemotherapyTo date, few treatment studies of chemoresistant NHL associated with HIV infection have been published. In general, the prognosis is very poor, and one should choose not to treat, to administer palliative chemotherapy or to consider experimental treatments.Antiretroviral treatment during chemotherapyIn HIV-infected patients with lymphoma, cART has independently contributed to improving the response to chemotherapy and survival.<a class="elsevierStyleCrossRefs" href="#bib1440">102–105</a> For this reason, all HIV-infected patients with NHL should receive cART simultaneously with chemotherapy.A cART regimen should be selected taking into account the antiretroviral treatment history, the HIV strain sensitivity, the HLA-B5701 result and the hepatitis B virus (HBV) infection markers. In some cases, it is recommended to have the tropism result of the HIV strain (R5, X4 or dual tropism). It is also important to always consider the potential pharmacological interactions and cross-toxicity between antiretrovirals and antitumor drugs or other drugs commonly used in this type of patient, such as antifungals.There is little clinical information about the effectiveness and safety of treatment with chemotherapy and antiretrovirals. In a series of 150 HIV-infected patients with cancer (mostly haematological malignancies) it was observed that the cART regimens based on protease inhibitors (PI) were less effective and less safe than those based on non-nucleoside reverse transcriptase inhibitors (NNRTI) and integrase strand transfer inhibitor (INSTI).<a class="elsevierStyleCrossRef" href="#bib1460">106</a> In addition, INSTI-based regimens were mostly chosen by clinicians when potentially significant interactions were anticipated between antiretrovirals, chemotherapeutic agents and other drugs such as antifungals.Between 40% and 60% of HIV-infected patients have been exposed to HBV, and between 3% and 10% have chronic hepatitis B defined by the presence of HBV surface antigen (HBsAg).<a class="elsevierStyleCrossRefs" href="#bib1465">107–109</a> Reactivation of HBV can occur during chemotherapy,<a class="elsevierStyleCrossRefs" href="#bib1480">110,111</a> especially when rituximab forms part of the therapeutic regimen.<a class="elsevierStyleCrossRef" href="#bib1490">112</a> Patients coinfected with HIV/HBV should receive a cART regimen that is also active against HBV (AI). Treatment should include tenofovir and emtricitabine (FTC) or lamivudine (3TC) along with a third active drug against HIV<a class="elsevierStyleCrossRef" href="#bib1495">113</a> (AI). Of the two existing tenofovir formulations, tenofovir alafenamide (TAF) should preferably be used, since it has a better safety profile than tenofovir disoproxil fumarate (TDF) and has the same activity against HBV.<a class="elsevierStyleCrossRefs" href="#bib1500">114–116</a>Pharmacological interactions between antiretroviral and antitumor drugsBoth PIs (especially ritonavir), cobicistat pharmacokinetic enhancer, and NNRTIs are metabolized in the liver and may be inhibitors or inducers of the CYP3A4 isoenzyme. Therefore, these antiretroviral drugs can alter the pharmacokinetics of antitumor drugs that are substrates of this isoenzyme, especially taxanes and alkylating agents such as cyclophosphamide and etoposide, and to a lesser extent, vinca alkaloids, antitumor antibiotics and platinum. There are no relevant interactions between antiretrovirals and anthracyclines because they are metabolized by the aldo-cetorreductase enzyme. Decreased clearance of cyclophosphamide and increased frequency of severe anaemia and neutropenia have been reported in patients receiving CHOP and cART compared with patients only treated with CHOP,<a class="elsevierStyleCrossRef" href="#bib1515">117</a> as well as severe cases of neutropenia and mucositis in patients receiving concomitant chemotherapy based on cyclophosphamide, doxorubicin and etoposide, and PI-based cART.<a class="elsevierStyleCrossRef" href="#bib1520">118</a> Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) have little potential for pharmacokinetic interaction with cytostatics. Maraviroc, a CCR5 receptor antagonist, is a substrate for the CYP3A enzyme and the P glycoprotein. For this reason, levels of maraviroc could be modified in the presence of potent CYP3A inducers or inhibitors. INSTI (raltegravir and dolutegravir) are metabolized in the liver by glucuronidation and have little interaction with cytostatic drugs. Elvitegravir, a third drug in this family, needs to be co-administered with the cobicistat enhancer, so that for all purposes their interactions are similar to those of the PI. No pharmacokinetic interactions have been described between antiretrovirals and rituximab, the most widely used monoclonal antibody for the treatment of NHL.<a class="elsevierStyleCrossRef" href="#bib1525">119</a> Recently, a comprehensive review of antiretroviral and antitumor interactions has been published,<a class="elsevierStyleCrossRef" href="#bib1530">120</a> an aspect that can also be consulted on specialized web pages.Cross toxicitiesWhen choosing a cART regimen, it is also very important to consider the safety profile of the drugs. Currently, the most used NRTIs for the treatment of HIV are 3TC, FTC, abacavir (AUC) and TDF or TAF. 3TC, FTC, TDF and TAF are also active drugs against HBV. 3TC, FTC and ABC lack cross-toxicity with antineoplastic drugs. TDF can produce proximal tubular nephropathy and decreased glomerular filtration rate,<a class="elsevierStyleCrossRef" href="#bib1535">121</a> and for this reason the use of TDF should be avoided in patients with renal insufficiency, tumour lysis syndrome or in those who receive antitumor drugs with nephrotoxic potential. TAF is equivalent in efficacy to TDF and lacks nephrotoxic potential, at least in the short term.<a class="elsevierStyleCrossRef" href="#bib1540">122</a> There are other NRTIs that are barely used today, such as zidovudine (AZT), didanosine (ddI) and stavudine (d4T), which present significant cross-toxicity with some antitumor drugs. AZT has myelotoxic potential and may enhance the haematological toxicity of different chemotherapeutic regimens. ddI and d4T can produce mitochondrial toxicity and can enhance the peripheral neuropathy characteristic of some antitumor drugs such as platinum, taxanes and vinca alkaloids.<a class="elsevierStyleCrossRef" href="#bib1530">120</a>Some PIs, such as atazanavir, lopinavir and saquinavir, may prolong the CT interval, which should be taken into account if they are administered together with antineoplastic drugs such as anthracyclines, which are also associated with prolongation of the CT interval. In patients with hepatopathy, bilirubin levels can be used to adjust the dose of some antitumor drugs. In these cases, treatment with atazanavir can make this adjustment difficult, given that this antiretroviral is frequently associated with unconjugated hyperbilirubinemia by inhibition of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1).Recommendations<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.HIV-infected patients with NHL should receive cART concomitantly with chemotherapy (AII).</li><li class="elsevierStyleListItem" id="lsti0010">2.The cART regimens of choice in patients with NHL receiving chemotherapy treatment are those based on an INSTI such as raltegravir (with which there is more experience) or dolutegravir, in combination with AUC/3TC or FTC/TAF (AII).</li><li class="elsevierStyleListItem" id="lsti0015">3.Treatment with other antiretroviral drugs may be indicated in some circumstances. The use of PI and cobicistat should be avoided as much as possible due to the frequency of their drug interactions. The use of TDF should also be avoided in patients with circumstances that increase the risk of renal toxicity (BII).</li><li class="elsevierStyleListItem" id="lsti0020">4.In the presence of HBV infection, the therapeutic regimen should include FTC/TAF as a preferred regimen or FTC/TDF as an alternative (AI).</li></ul>Complementary treatmentsSupportive treatment for tumour lysis syndromePatients with large tumour mass may present complications derived from the tumour lysis syndrome at the time of diagnosis or after starting chemotherapy. In cases in which this complication is foreseeable, due to tumour volume or very high levels of LDH and uric acid, the administration of chemotherapy should be preceded by a preventive treatment with hyperhydration, forced diuresis and administration of allopurinol. You can also use rasburicase, a recombinant form of the urate oxidase enzyme that converts uric acid into allantoin, which is eliminated more easily by the kidneys. This drug is more effective than allopurinol in reducing the plasma levels of uric acid and can prevent excessive delay in the start of chemotherapy.<a class="elsevierStyleCrossRefs" href="#bib1545">123,124</a> The recommended dose of rasburicase is 0.20mg/kg/day intravenously in 50ml of normal saline for 30min. The duration of treatment ranges from 5 to 7 days, although the shorter duration regimens seem equally effective.Colony-stimulating factorsThe administration of granulocyte colony stimulating factors (G-CSF) is recommended to shorten the duration of post-chemotherapy neutropenia, to counteract the poor tolerance to cytostatics and to be able to use full doses and adequate intervals of chemotherapy (AI).<a class="elsevierStyleCrossRef" href="#bib1555">125</a> Filgrastim at a dose of 5μg/kg on days 7–12 is recommended with CHOP. The same doses will be administered with EPOCH from day 6° of the cycle to achieve an absolute number of neutrophils greater than 1×109/l for two consecutive days. With CODOX-M/IVAC, the treatment with filgrastim should be started on day 13 of the A regimen and on the day 7 of the B regimen until the next cycle or until you get a neutrophil count greater than 1×109/l. If other therapeutic regimens are used, its use will be adapted to them.Prophylaxis of opportunistic infections associated with HIV infectionAfter the administration of chemotherapy, the total number of CD4+ T lymphocytes decreases in 30–50% with respect to the baseline, depending on the intensity of the treatment and the moment in which the analysis is carried out. This is the reason why in these patients the risk of opportunistic infections associated with HIV is greater than in patients without NHL in a similar stage. In principle, it should be said that primary or secondary prophylaxis that are the indicated according to the CD4+ T lymphocyte count and the previous history of opportunistic infections<a class="elsevierStyleCrossRef" href="#bib1560">126</a> should be performed, although it is recommended to consider that the degree of immunosuppression of patients is greater than the one shown by the CD4+ T lymphocyte count at the time of tumour diagnosis and that these lymphocyte markers should be monitored throughout the treatment of the lymphoma, acting accordingly. Pneumocystis jirovecii prophylaxis is recommended for all patients (AII). Anti-CMV prophylaxis is generally not recommended, but close monitoring with periodic blood PCR determinations for this virus in those patients with a CD4+ T lymphocyte count <100/mm is recommended.<a class="elsevierStyleCrossRef" href="#bib0945">3</a> In cases in which CMV viraemia is detected, fundoscopy should be performed to rule out retinitis, and regardless of the result, the administration of anti-CMV treatment should be considered.Prophylaxis and treatment of infections associated with neutropeniaNeutropenia, a common complication during the treatment of lymphoma, is a well-known risk factor for serious bacterial and fungal infections. In patients with fever and neutropenia, empirical antibiotic treatment should be started without delay after taking blood and urine cultures (A1).<a class="elsevierStyleCrossRefs" href="#bib1565">127–129</a> Antibiotic prophylaxis is a controversial issue in this group of patients. Prophylaxis is considered acceptable in some guidelines with patients who have high-risk factors for infection, such as those receiving intensive chemotherapy regimens or recipients of HSCT, in whom deep and prolonged neutropenia is frequent (≤100neutrophils/mm3 during >7 days). However, we must take into account the effects that this practice can have, if carried out systematically, on antibiotic resistance and other undesirable effects, such as Clostridium difficile colitis.VaccinationsAnnual inactivated influenza vaccination is indicated both in patients with HIV infection and in patients with lymphoma. In the case of the latter, influenza vaccination of close contacts is also recommended (AI).<a class="elsevierStyleCrossRef" href="#bib1580">130</a> Although the optimal time to administer the influenza vaccine is unknown, it is recommended to administer it at least 2 weeks before starting chemotherapy or at least one week after the last cycle (B-III).<a class="elsevierStyleCrossRef" href="#bib1570">128</a> These patients, like all those infected with HIV, should also receive vaccination against pneumococcus, HBV and hepatitis A virus.<a class="elsevierStyleCrossRefs" href="#bib1585">131,132</a>Primary lymphoma of the central nervous system associated with HIV infectionPCNSL is an NHL limited to the craniospinal axis, in most cases of B lineage.<a class="elsevierStyleCrossRef" href="#bib1595">133</a> Its incidence increased considerably with the AIDS epidemic, although it experienced a significant decrease after the introduction of cART. In the early years of the epidemic, the prognosis of PCNSL associated with HIV infection was very poor, with median survival around 3 months or slightly more after receiving radiotherapy. The prognosis has improved with cART, which has allowed a better virologic control, immunological improvement and decrease in the incidence of opportunistic infections. These recommendations will emphasize two clinical aspects of PCNSL associated with HIV infection: the diagnostic procedure and the most appropriate antitumor treatment.DiagnosisIn patients with HIV infection, PCNSL usually occurs in highly immunosuppressed patients, with CD4+ T lymphocyte values less than 50/mm3, and it constitutes an AIDS-defining disease in approximately a third of cases. There is no clinical data that is specific to this tumour, so this diagnosis should be considered in HIV-infected patients with CNS involvement. The context in which both PCNSL and cerebral toxoplasmosis occur, and the similarity of their clinical and radiological manifestations means that the differential diagnosis between both diseases is frequently raised. In these cases, it is useful to have imaging tests (CT or MRI) and to know the CD4+ T lymphocyte count and the result of serology (IgG) for Toxoplasma gondii.Cranial computed tomographyCranial CT is the most used initial imaging test in patients with HIV infection and neurological manifestations, but PCNSL lesions can be indistinguishable from those of toxoplasmosis. In the first case, there is one single lesion and usually large. They are normally necrotic masses, occasionally haemorrhagic, poorly-defined, with irregular margins, with variable mass effect, peritumoral oedema and ring-shaped contrast uptake. The site of the lesions is not an absolutely differentiating criterion either. Although lesions of PCNSL are preferably supratentorial and often infiltrate deep structures (periventricular regions, thalamus, basal lymph nodes and corpus callosum), they can also be located in the periphery of the cerebral hemispheres.<a class="elsevierStyleCrossRef" href="#bib1595">133</a>Cranial magnetic resonance imagingMRI is more sensitive than CT when the lesions are small and allows to define them better when they are located in the leptomeninges or the spinal canal. However, the specificity of both tests is not very different. There are techniques that can improve the diagnostic performance of MRI, such as dynamic MRI and MR spectroscopy (MRS). In dynamic MRI, gadolinium uptake in T1 sequences is faster and more intense in PCNSL than in toxoplasmosis. In MRS, the spectrum of the lesion can be compared with that of healthy tissue, identifying peaks of biochemical metabolites characteristic of certain diseases.<a class="elsevierStyleCrossRefs" href="#bib1600">134,135</a>Single photon emission tomography and cranial positron emission tomographyNuclear medicine techniques, such as single photon emission tomography (SPECT) with thallium-201 and PET, can help in the differential diagnosis. SPECT studies with thallium-201 performed in patients with PCNSL show a lesion uptake because there is an active transport of thallium-201 inside the neoplastic cells, which does not happen in cerebral toxoplasmosis. SPECT with thallium-201 has some limitations, since it does not detect lesions smaller than 6mm or leptomeningeal lesions or near the cranial base or the calotte. In addition, glucocorticoids can stabilize thallium uptake. For the diagnosis of PCNSL, SPECT has a sensitivity of 75% and a specificity of 97% and, in the opinion of some authors, a positive result would be an indication of performing an early stereotactic brain biopsy. In other studies, the diagnostic yield of the technique has been improved through the assessment of early or late uptake and the calculation of the thallium retention index.<a class="elsevierStyleCrossRef" href="#bib1610">136</a> PET uses metabolites such as 18 fluorodeoxyglucose (FDG), which is captured by cells with high metabolic activity and high energy consumption, such as malignant cells. The diagnostic role of PET for the diagnosis of PCNSL is not totally clear.<a class="elsevierStyleCrossRef" href="#bib1615">137</a>Analysis of cerebrospinal fluidCSF analysis can help the diagnosis of PCNSL, so it should be done as long as it does not pose a risk to the patient. When there is a periventricular or meningeal condition, tumour cells can be identified in the CSF. By means of cytofluorometry, in situ hybridization or polymerase chain reaction (PCR), populations of monoclonal lymphocytes of a neoplastic nature and sequences of the Epstein-Barr virus (EBV) genome can be detected in the nucleus of said cells. In some studies, a good diagnostic correlation has been observed between stereotactic brain biopsy and PCR for EBV in CSF, especially in patients with negative serology. T. gondii and single radiological lesion.<a class="elsevierStyleCrossRefs" href="#bib1615">137–139</a> However, most patients with PCNSL require a diagnosis by biopsy.Brain biopsyStereotactic brain biopsy is the diagnostic technique of choice. When carried out by experienced teams, it allows to establish the diagnosis in 96% of cases, with few complications.<a class="elsevierStyleCrossRef" href="#bib1630">140</a> In a recent meta-analysis, the morbidity of this procedure in patients with PCNSL was 5.1%, with bleeding being the most common complication.<a class="elsevierStyleCrossRef" href="#bib1635">141</a>Practical recommendations for the diagnosis of primary central nervous system lymphomaIn patients with HIV infection and space-occupying lesions (SOL) on CT or MRI, Toxoplasma serology should be performed and a CD4+ T lymphocyte determination. Different situations can occur.If there is a single lesion or the Toxoplasma serology is negative and if the situation of the patient and the type of injury allow it, a lumbar puncture should be performed with study of CSF cytocentrifugate and cytofluorometry, as well as a PCR for EBV and Toxoplasma. The sum of positive tests suggestive of PCNSL (including cytology and PCR for CSF EBV) would strongly support the diagnosis, but this should be established by brain biopsy. It is important to keep in mind that anti-Toxoplasma empirical treatment should be administered until diagnostic confirmation is achieved.When the lesions are multiple, and the Toxoplasma serology is positive, empirical anti-Toxoplasma treatment must be administered during 2 weeks. If after this period there is resolution or clinical and radiological improvement, the diagnosis of cerebral toxoplasmosis can be assumed. Otherwise, a stereotactic brain biopsy should be performed as soon as possible.Treatment of primary central nervous system lymphomaAt present, it is not known which the best treatment for PCNSL in a HIV-infected patient is. However, considering the better prognosis of these patients with the new antiretroviral treatments, the treatment regimens used in patients without HIV infection could be adopted.In general, the best therapeutic results in PCNSL have been achieved with high doses of methotrexate (MTX-HA) alone or in combination with other drugs. Radiation therapy has important neurological toxicity, especially in elderly patients, and is currently reserved for salvage therapy or patients with very poor general condition who cannot receive chemotherapy.RadiotherapyRadiotherapy has been the treatment of choice for PCNSL for many years and, although it can provide short-term improvements, relapses are frequent. In a prospective trial of the Radiation Therapy Oncology Group (RTOG-8315) the median survival after radiotherapy in patients with PCNSL was one year.<a class="elsevierStyleCrossRef" href="#bib1640">142</a> In patients with PCNSL associated with HIV infection, the median survival has varied between 72 and 119 days,<a class="elsevierStyleCrossRefs" href="#bib1645">143–145</a> although slightly higher survivals have been documented in patients treated with cART.<a class="elsevierStyleCrossRef" href="#bib1660">146</a><a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the radiotherapy treatment of PCNSL based on recent publications.Combined radiotherapy and chemotherapy treatmentTo date, all clinical trials with combined radiotherapy and chemotherapy have been conducted in patients with PCNSL not associated with HIV infection. In four clinical trials of treatment with chemotherapy based on MTX-HD and radiotherapy, significant neurotoxicity was observed, especially in older patients, with median survival between 37 and 46 months.<a class="elsevierStyleCrossRefs" href="#bib1665">147–150</a> Another clinical trial with 551 newly diagnosed patients who were randomized to treatment with chemotherapy based on MTX-HD with or without holocranial radiotherapy, radiotherapy did not demonstrate a prognosis improvement in patients.<a class="elsevierStyleCrossRef" href="#bib1685">151</a> The published experience with this therapeutic strategy in patients with PCNSL associated with HIV infection is limited to retrospective series with a small number of cases.<a class="elsevierStyleCrossRef" href="#bib1690">152</a>ChemotherapyMTX is the most effective and most used cytostatic in the treatment of PCNSL. In a study with non-HIV-infected patients, monotherapy with MTX-HD (3–8g/m2) has had CR in 52% of cases, with a median survival of 55.4 months, with little toxicity.<a class="elsevierStyleCrossRef" href="#bib1695">153</a> In a clinical trial comparing monotherapy with MTX-HD versus combined treatment with MTX-HD and cytosine arabinoside (AraC) that did not include patients with HIV infection, the overall response was higher in the combined treatment arm (40% vs 69%, p=0.009), group in which haematological toxicity was also observed more frequently.<a class="elsevierStyleCrossRef" href="#bib1700">154</a> The available data for patients with PCNSL associated with HIV infection are limited. The results of a large retrospective series of patients with PCNSL treated between 1988 and 2012 suggest that the results in the era of cART with MTX-HD-based chemotherapy (with or without rituximab) are superior to the results of the pre-cART era, in which patients were treated mostly with radiotherapy.<a class="elsevierStyleCrossRef" href="#bib1705">155</a> The median survival in a prospective series of 15 patients treated with 6 cycles of MTX-HD (3g/m2) was 290 days.<a class="elsevierStyleCrossRef" href="#bib1710">156</a> In a second prospective study with 12 patients who received different MTX-HD regimens (between 3 and 8g/m2), the median survival exceeded 50 months.RituximabThere are retrospective studies in patients with PCNSL with or without HIV infection suggesting that the addition of rituximab could provide an additional benefit.<a class="elsevierStyleCrossRefs" href="#bib1700">154,155,157</a> A pilot study of treatment with MTX-HD associated with rituximab is currently being conducted in patients with PCNSL associated with HIV infection.Chemotherapy associated with an autologous hematopoietic stem cell transplantThere are at least three prospective studies of sequential treatment with MTX-HD based chemotherapy followed by consolidation with autologous HSCT in patients with PCNSL without HIV infection suggesting that this therapeutic modality is feasible and can provide prolonged survival with preserved neurocognitive function and good post-transplant quality of life.<a class="elsevierStyleCrossRefs" href="#bib1720">158–161</a>Antiretroviral treatmentAntiretroviral treatment regimens, anti-infective prophylaxis or other complementary treatments are the same as those indicated for systemic lymphoma.Practical recommendations for the treatment of primary central nervous system lymphomaAlthough there are few studies of PCNSL treatment in patients with HIV infection, it is recommended to use the same treatments as for patients without HIV infection (AII). Patients with good general condition should be treated with one of the MTX-HD-based chemotherapy regimens designed for this tumour, preferably accompanied by rituximab (AII). The preferred chemotherapy regimen is the combination of MTX-HD and Ara-C (AI). Consolidation with autologous HSCT (CII) can be considered in some patients. Radiotherapy should be considered when chemotherapy has failed or is contraindicated (BII). All patients should receive cART and the anti-infective prophylaxis that are indicated (AI).Hodgkin's lymphomaThe clinical presentation of HL in HIV-infected patients has changed significantly after the introduction of cART. During the first years of the epidemic, patients frequently presented with advanced stages or with atypical manifestations as primary extranodal forms. Although the clinical presentation also seems to have undergone some changes, the characteristics of HL in HIV-positive patients remain more aggressive than in the general population.<a class="elsevierStyleCrossRef" href="#bib1740">162</a> The introduction of cART has also meant a radical change in the prognosis of HIV-infected patients and HL, and information from different series shows that at present the prognosis of these patients can be compared to that of patients without HIV infection.<a class="elsevierStyleCrossRefs" href="#bib1745">163–165</a>Diagnosis, extension study and factors related to the prognosisThe same criteria mentioned in the NHL section on the need for a histological study of a complete lymph node or a broad biopsy of infiltrated tissue are applied with HL. The same applies to the complementary tests for the extension study, with special emphasis on performing a baseline PET-CT study for all patients. In contrast, the bone marrow study would only be indicated when there is a high suspicion of infiltration, such as when peripheral cytopenia is detected. The Hasenclever index, commonly used to estimate the prognosis of patients with advanced HL,<a class="elsevierStyleCrossRef" href="#bib1760">166</a> also applies to patients with HIV infection.<a class="elsevierStyleCrossRefs" href="#bib1765">167,168</a> This system includes 7 factors, each of which reduces the probability of disease control to 5 years by 7–8% (age ≥45 years, male, staging IV, albumin <4g/dl, haemoglobin <10.5g/dl, leukocytes ≥15×109/ and lymphocytes <0.6×109/l (<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>).<elsevierMultimedia ident="tbl0030"></elsevierMultimedia>TreatmentIn the era of cART, the results of the treatment of HL in patients with HIV infection with chemotherapy regimens normally used in the treatment of this tumour (ABVD, Stanford V or BEACOPP) do not differ substantially from those obtained in the general population (AI).<a class="elsevierStyleCrossRefs" href="#bib1745">163,164,167,169–171</a> For this reason, in patients with HIV infection and HL, the same recommendations should be followed for the first-line treatment of this tumour indicated for the general population.<a class="elsevierStyleCrossRef" href="#bib1790">172</a>For patients with HIV infection and HL refractory to a first-line chemotherapy or relapse, salvage therapy should be identical to that of the general population not infected with HIV: second-line chemotherapy with ESHAP, DHAP or ICE type regimens, among others, and in case of chemosensitivity, consolidation with autologous HSCT.<a class="elsevierStyleCrossRef" href="#bib1425">99</a> Exceptionally, in selected cases, the implementation of an allogeneic HSCT with reduced intensity conditioning could be considered.In patients with refractory or relapsed HL after autologous HSCT, treatments with new forms of immunotherapy can be proposed, particularly brentuximab vedotin.<a class="elsevierStyleCrossRef" href="#bib1795">173</a> Currently, clinical trials are underway to determine the role of brentuximab in combination with chemotherapy in HIV-infected patients with HL. Although no information is available on the efficacy of PD-1/PDL-1 inhibitors (Programmed cell death protein 1/Programmed death-ligand 1) in HIV-infected patients with relapsed HL, there is enough information to support its efficacy in patients with HL who are not infected with HIV.<a class="elsevierStyleCrossRef" href="#bib1800">174</a><a class="elsevierStyleCrossRef" href="#tbl0035">Table 7</a> lists the practical recommendations for the treatment of HL in HIV-infected population. It is important to bear in mind that these patients must follow the same recommendations on cART and complementary treatments applicable to patients with HIV infection and NHL.<elsevierMultimedia ident="tbl0035"></elsevierMultimedia>Hematopoietic stem cell transplantationAutologous transplantIn patients with systemic NHL in first relapse and sensitive to chemotherapy, without HIV infection, the administration of high doses of chemotherapy, with or without radiotherapy, followed by an autologous HSCT, is considered the treatment of choice for their rescue.Different national and international groups have published their experience in autologous HSCT in patients with HIV infection.<a class="elsevierStyleCrossRefs" href="#bib1425">99,175–179</a> The results of all these studies allow us to conclude that autologous HSCT in HIV-infected patients with HL or NHL receiving cART is a viable, safe and effective procedure, with which no greater toxicity inherent to the procedure has been observed nor a substantial increase of infectious complications, when compared with the group of patients with lymphoma without HIV infection. Therefore, autologous HSCT in this population group should be considered for the same indications as for the general population with this type of tumours (<a class="elsevierStyleCrossRef" href="#tbl0040">Table 8</a>).<elsevierMultimedia ident="tbl0040"></elsevierMultimedia>From the accumulated experience of the aforementioned studies, the following considerations can be made about autologous HSCT in HIV-infected patients:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025">1.The current legal regulations regarding the specific handling and storage of hematopoietic stem cells with risk of infection transmission must be applied.</li><li class="elsevierStyleListItem" id="lsti0030">2.Mobilization of hematopoietic stem cells in these patients is similar to that obtained in patients without HIV infection.</li><li class="elsevierStyleListItem" id="lsti0035">3.The haematological and immunological recovery in these patients is comparable to that observed in patients without HIV infection and the use of G-CSF is recommended until the engraftment.</li><li class="elsevierStyleListItem" id="lsti0040">4.cART must be maintained during mobilization and HSCT, avoiding antiretroviral myelotoxic drugs.</li><li class="elsevierStyleListItem" id="lsti0045">5.The toxicity-related mortality rate is similar to that observed in non-HIV-infected patients.</li><li class="elsevierStyleListItem" id="lsti0050">6.In the conditioning of autologous HSCT in lymphoma with involvement of the CNS, it is recommended to include thiotepa and BCNU (HF).<a class="elsevierStyleCrossRef" href="#bib1830">180</a></li></ul>Allogeneic hematopoietic stem cell transplantationAllogeneic HSCT has a high toxicity-related mortality (20–30%, compared to 5% in autologous HSCT), which is why it has traditionally been indicated in selected patients, with good general condition, in whom an autologous HSCT could not be carried out due to insufficient mobilization of hematopoietic stem cells and that had a family donor with identical histocompatibility antigens. In patients with HIV infection, the experience with allogeneic HSCT is more limited than with autologous HSCT, but it has been spreading in recent years, including the use of alternative donors.<a class="elsevierStyleCrossRefs" href="#bib1835">181–186</a>The indications and procedures of allogeneic HSCT in these patients are similar to those used in patients without HIV infection. However, several aspects must be taken into special consideration in this population:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0055">1.Toxicity-related mortality is higher than in patients without HIV infection, so the procedure should be carried out in centres with experience in HSCT in high-risk patients and in close collaboration with professionals with experience in the treatment of HIV infection.</li><li class="elsevierStyleListItem" id="lsti0060">2.Supportive treatment is very important and should include adequate anti-infective prophylaxis and close follow-up after transplantation due to the high risk of mortality associated with infections, especially in patients with active graft-versus-host disease.</li><li class="elsevierStyleListItem" id="lsti0065">3.cART must be maintained throughout the procedure.</li><li class="elsevierStyleListItem" id="lsti0070">4.cART of choice is indicated in the corresponding section of these guidelines.</li></ul>Stem cell transplantation and HIV eradicationAllogeneic hematopoietic stem cell transplantation carrying the homozygous mutation for the Δ32 deletion of the chemokine receptor CCR5 (which makes the cell resistant to HIV entry with tropism R5) has allowed the eradication of HIV from a patient with high-risk leukaemia in which there is no evidence of virus presence after 8 years of sustained ART discontinuation.<a class="elsevierStyleCrossRef" href="#bib1840">182</a> This case, known as the “Berlin patient”, illustrates that it is possible to cure HIV infection. In addition, the study of the possible mechanisms involved in the eradication of HIV in this patient has served to advance in different aspects related to the cure of this viral infection.<a class="elsevierStyleCrossRef" href="#bib1855">185</a> Therefore, although the choice of the donor in patients with HIV infection in whom allogeneic transplantation is indicated should be carried out following the same criteria as in patients without HIV infection, it is recommended to explore the availability of a source of stem cells with a homozygous mutation for the Δ32 deletion of the chemokine receptor CCR5 as a possible strategy for the cure of HIV infection.FundingSpanish AIDS Research Network (RIS). Cooperative Health Research Networks (RETICS), projects RD16/0025/0017 and RD12/0036/0029, as part of the National Plan R+D+I co-financed by ISCIII-General Evaluation Subdirectorate and the European Regional Development Fund (ERDF).Conflict of interestThe authors declare no conflict of interest." 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"identificador" => "sec0275" "titulo" => "Treatment" ] ] ] 11 => array:3 [ "identificador" => "sec0280" "titulo" => "Hematopoietic stem cell transplantation" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0285" "titulo" => "Autologous transplant" ] 1 => array:2 [ "identificador" => "sec0290" "titulo" => "Allogeneic hematopoietic stem cell transplantation" ] 2 => array:2 [ "identificador" => "sec0295" "titulo" => "Stem cell transplantation and HIV eradication" ] ] ] 12 => array:2 [ "identificador" => "sec0300" "titulo" => "Funding" ] 13 => array:2 [ "identificador" => "sec0305" "titulo" => "Conflict of interest" ] 14 => array:2 [ "identificador" => "xack359056" "titulo" => "Acknowledgements" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-08-16" "fechaAceptado" => "2017-11-02" "PalabrasClave" => array:2 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1009613" "palabras" => array:5 [ 0 => "Non-Hodgkin's lymphoma" 1 => "Hodgkin's lymphoma" 2 => "HIV" 3 => "AIDS" 4 => "Antiretroviral therapy" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1009612" "palabras" => array:76 [ 0 => "ABC" 1 => "ABVD" 2 => "Ara-C" 3 => "AZT" 4 => "BCNU" 5 => "BEACOPP" 6 => "CDC" 7 => "CHOP" 8 => "CMV" 9 => "CODOX-M/IVAC" 10 => "d4" 11 => "dd" 12 => "DH" 13 => "DHAP" 14 => "MCD" 15 => "EPOCH" 16 => "AD-EPOCH-R EPOCH-R" 17 => "MRS" 18 => "ESHAP" 19 => "FDG18" 20 => "FTC" 21 => "G-CSF" 22 => "GESID" 23 => "Gy" 24 => "HBs" 25 => "HHV-8" 26 => "Hyper-CVAD" 27 => "ICE" 28 => "IL-6" 29 => "IMRT" 30 => "INSTI" 31 => "PI" 32 => "IPI" 33 => "IT" 34 => "NRTI" 35 => "NNRTI" 36 => "LANA-1" 37 => "BL" 38 => "DLBCL" 39 => "CSF" 40 => "LDH" 41 => "HL" 42 => "LMP1" 43 => "NHL" 44 => "SOL" 45 => "PCNSL" 46 => "Lymphomatous LM" 47 => "MTX" 48 => "MTX-HD" 49 => "PCR" 50 => "PD-1/PDL-1" 51 => "PET-CT" 52 => "PETHEM" 53 => "CT" 54 => "R-CHOEPR-CHOP" 55 => "R-CHOP" 56 => "R-EPOCH" 57 => "CR" 58 => "RT" 59 => "MRI" 60 => "OS" 61 => "KS" 62 => "EFS" 63 => "SNC" 64 => "SPECT" 65 => "Stanford V" 66 => "TAF" 67 => "cART" 68 => "TDF" 69 => "TH" 70 => "HSCT" 71 => "3TC" 72 => "UGT1A1" 73 => "EBV" 74 => "HBV" 75 => "HIV" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1009614" "palabras" => array:5 [ 0 => "Linfoma no hodgkiniano" 1 => "Linfoma de Hodgkin" 2 => "VIH" 3 => "Sida" 4 => "Tratamiento antirretroviral" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The incidence of non-Hodgkin's lymphoma and Hodgkin's lymphoma is higher in patients with HIV infection than in the general population. Following the introduction of combination antiretroviral therapy (cART), the prognostic significance of HIV-related variables has decreased, and lymphoma-related factors have become more pronounced. Currently, treatments for lymphomas in HIV-infected patients do not differ from those used in the general population. However, differentiating characteristics of seropositive patients, such as the need for cART and specific prophylaxis and treatment of certain opportunistic infections, should be considered. This document updates recommendations on the diagnosis and treatment of lymphomas in HIV infected patients published by GESIDA/PETHEMA in 2008." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La incidencia de linfoma no hodgkiniano y linfoma de Hodgkin es mayor en pacientes con infección por el VIH que en la población general. Tras la introducción del tratamiento antirretroviral de combinación (TARc) ha disminuido la importancia pronóstica de variables relacionadas con el VIH, adquiriendo mayor peso factores relacionados con el linfoma. Actualmente, los tratamientos de los linfomas en pacientes infectados por VIH no difieren de los empleados en la población general. Pero existen algunos aspectos diferenciales de los pacientes con VIH como la necesidad de TARc, de profilaxis y de tratamientos de algunas infecciones oportunistas. En este documento se actualizan las recomendaciones sobre el diagnóstico y el tratamiento de los linfomas en pacientes infectados por VIH publicadas por GESIDA/PETHEMA en 2008." ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Miralles P, Navarro JT, Berenguer J, Gómez Codina J, Kwon M, Serrano D, et al. Recomendaciones de GESIDA/PETHEMA sobre el diagnóstico y tratamiento de los linfomas en pacientes infectados por el virus de la inmunodeficiencia humana. Med Clin (Barc). 2018;151:39.e1–39.e17." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "This document is endorsed by the GESIDA groups (attached to the Spanish Society of Infectious Diseases and Clinical Microbiology) and PETHEMA (attached to the Spanish Society of Haematology and Hemotherapy)." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:3 [ 0 => array:4 [ "apendice" => "<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0075">•B-cell neoplasms<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0080">I.Precursor B-cell neoplasms<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0085">-Leukaemia/lymphoblastic lymphoma B</li></ul></li><li class="elsevierStyleListItem" id="lsti0090">II.Mature B-cell neoplasms<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0095">-B-cell chronic lymphocytic leukaemia/small cell lymphocytic lymphoma</li><li class="elsevierStyleListItem" id="lsti0100">-B-cell prolymphocytic leukaemia</li><li class="elsevierStyleListItem" id="lsti0105">-Splenic marginal zone lymphoma</li><li class="elsevierStyleListItem" id="lsti0110">-Tricholeukemia</li><li class="elsevierStyleListItem" id="lsti0115">-Leukaemia/splenic B-cell lymphoma, unclassifiable</li><li class="elsevierStyleListItem" id="lsti0120">-Splenic diffuse red pulp small b-cell lymphoma</li><li class="elsevierStyleListItem" id="lsti0125">-Variant of circulating villous lymphocytes</li><li class="elsevierStyleListItem" id="lsti0130">-Lymphoplasmacytic lymphoma and Waldenström macroglobulinemia</li><li class="elsevierStyleListItem" id="lsti0135">-Heavy-chain diseases</li><li class="elsevierStyleListItem" id="lsti0140">-Alpha heavy chain disease</li><li class="elsevierStyleListItem" id="lsti0145">-Gamma heavy chain disease</li><li class="elsevierStyleListItem" id="lsti0150">-Mu heavy chain disease</li><li class="elsevierStyleListItem" id="lsti0155">-Plasma cell neoplasms</li><li class="elsevierStyleListItem" id="lsti0160">-Monoclonal gammopathy of uncertain significance</li><li class="elsevierStyleListItem" id="lsti0165">-Plasma cell myeloma</li><li class="elsevierStyleListItem" id="lsti0170">-Solitary bone plasmacytoma</li><li class="elsevierStyleListItem" id="lsti0175">-Extraosseous plasmacytoma</li><li class="elsevierStyleListItem" id="lsti0180">-Extranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)</li><li class="elsevierStyleListItem" id="lsti0185">-Nodal marginal zone lymphoma</li><li class="elsevierStyleListItem" id="lsti0190">-Follicular lymphoma</li><li class="elsevierStyleListItem" id="lsti0195">-Primary cutaneous follicle centre lymphoma</li><li class="elsevierStyleListItem" id="lsti0200">-Mantle cell lymphoma</li><li class="elsevierStyleListItem" id="lsti0205">-Diffuse large B-cell lymphoma (DLBCL)<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0210">-DLBCL (without other specification)</li><li class="elsevierStyleListItem" id="lsti0215">-Morphological variants:</li><li class="elsevierStyleListItem" id="lsti0220">-Centroblastic</li><li class="elsevierStyleListItem" id="lsti0225">-Immunoblastic</li><li class="elsevierStyleListItem" id="lsti0230">-Anaplastic</li><li class="elsevierStyleListItem" id="lsti0235">-Other</li><li class="elsevierStyleListItem" id="lsti0240">-Molecular variants:</li><li class="elsevierStyleListItem" id="lsti0245">-Germinal centre</li><li class="elsevierStyleListItem" id="lsti0250">-Activated B-cells</li><li class="elsevierStyleListItem" id="lsti0255">-Specific subtypes:</li><li class="elsevierStyleListItem" id="lsti0260">-T-cell/histiocyte rich</li><li class="elsevierStyleListItem" id="lsti0265">-Primary central nervous system DLBCL</li><li class="elsevierStyleListItem" id="lsti0270">-Cutaneous DLBCL, leg type</li><li class="elsevierStyleListItem" id="lsti0275">-EBV-positive DLBCL of the elderly</li><li class="elsevierStyleListItem" id="lsti0280">-Other large B-cell lymphomas:</li><li class="elsevierStyleListItem" id="lsti0285">-Primary mediastinal DLBCL (thymic)</li><li class="elsevierStyleListItem" id="lsti0290">-Intravascular lymphoma</li><li class="elsevierStyleListItem" id="lsti0295">-DLBCL associated with chronic inflammation</li><li class="elsevierStyleListItem" id="lsti0300">-Lymphomatoid granulomatosis</li><li class="elsevierStyleListItem" id="lsti0305">-ALK-positive DLBCL</li><li class="elsevierStyleListItem" id="lsti0310">-Plasmablastic lymphoma</li><li class="elsevierStyleListItem" id="lsti0315">-DLBCL arising in HHV8-associated multicentric Castleman disease</li><li class="elsevierStyleListItem" id="lsti0320">-Effusion lymphoma</li><li class="elsevierStyleListItem" id="lsti0325">-Borderline cases:</li><li class="elsevierStyleListItem" id="lsti0330">-Unclassifiable B-cell lymphoma, with intermediate features between DLBCL and Burkitt's lymphoma</li><li class="elsevierStyleListItem" id="lsti0335">-Unclassifiable B-cell lymphoma, with intermediate features between DLBCL and classic Hodgkin's lymphoma</li><li class="elsevierStyleListItem" id="lsti0340">-Burkitt's lymphoma</li></ul></li></ul></li></ul></li></ul><ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0345">•T-cell and NK-cell neoplasms<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0350">I.Precursor T-cell neoplasms<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0355">-Leukaemia/T-cell lymphoblastic lymphoma</li></ul></li><li class="elsevierStyleListItem" id="lsti0360">II.Peripheral T-cell and NK-cell neoplasms<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0365">-T-cell prolymphocytic leukaemia</li><li class="elsevierStyleListItem" id="lsti0370">-T-cell large granular lymphocytic leukaemia</li><li class="elsevierStyleListItem" id="lsti0375">-Chronic lymphoproliferative disorder of NK cells</li><li class="elsevierStyleListItem" id="lsti0380">-Aggressive NK-cell leukaemia</li><li class="elsevierStyleListItem" id="lsti0385">-Systemic EBV+T cell lymphoproliferative disease of childhood</li><li class="elsevierStyleListItem" id="lsti0390">-Leukaemia/adult T-cell lymphoma</li><li class="elsevierStyleListItem" id="lsti0395">-Extranodal NK/T-cell lymphoma, nasal type</li><li class="elsevierStyleListItem" id="lsti0400">-T-cell lymphoma associated with enteropathy</li><li class="elsevierStyleListItem" id="lsti0405">-Hepatosplenic T-cell lymphoma</li><li class="elsevierStyleListItem" id="lsti0410">-Pancreatic subcutaneous T-cell lymphoma</li><li class="elsevierStyleListItem" id="lsti0415">-Mycosis fungoides</li><li class="elsevierStyleListItem" id="lsti0420">-Sézary syndrome</li><li class="elsevierStyleListItem" id="lsti0425">-T-cell lymphoproliferative disorders, cutaneous, CD30+</li><li class="elsevierStyleListItem" id="lsti0430">-Primary cutaneous anaplastic large-cell lymphoma</li><li class="elsevierStyleListItem" id="lsti0435">-Lymphomatoid papulosis</li><li class="elsevierStyleListItem" id="lsti0440">-Primary cutaneous peripheral T-cell lymphomas (rare forms)</li><li class="elsevierStyleListItem" id="lsti0445">-Primary cutaneous gamma/delta T-cell lymphoma</li><li class="elsevierStyleListItem" id="lsti0450">-Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma</li><li class="elsevierStyleListItem" id="lsti0455">-Primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma</li><li class="elsevierStyleListItem" id="lsti0460">-Peripheral T-cell lymphoma (without other specification)</li><li class="elsevierStyleListItem" id="lsti0465">-T-cell angioimmunoblastic lymphoma</li><li class="elsevierStyleListItem" id="lsti0470">-Anaplastic large cell lymphoma, ALK+</li><li class="elsevierStyleListItem" id="lsti0475">-Anaplastic large cell lymphoma, ALK−</li></ul></li></ul></li><li class="elsevierStyleListItem" id="lsti0480">•Hodgkin's lymphoma<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0485">-Nodular lymphocyte predominant Hodgkin's lymphoma</li><li class="elsevierStyleListItem" id="lsti0490">-Classic Hodgkin's lymphoma</li><li class="elsevierStyleListItem" id="lsti0495">-Nodular sclerosis</li><li class="elsevierStyleListItem" id="lsti0500">-Mixed cellularity</li><li class="elsevierStyleListItem" id="lsti0505">-Lymphocyte-rich</li><li class="elsevierStyleListItem" id="lsti0510">-Lymphocyte depletion</li></ul></li><li class="elsevierStyleListItem" id="lsti0515">•Post-transplant lymphoproliferative disorders (PTLD)<ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0520">-Early lesions</li><li class="elsevierStyleListItem" id="lsti0525">-Plasmacytic hyperplasia</li><li class="elsevierStyleListItem" id="lsti0530">-Infectious mononucleosis-like PTLD</li><li class="elsevierStyleListItem" id="lsti0535">-Polymorphic PTLD</li><li class="elsevierStyleListItem" id="lsti0540">-Monomorphic PTLD (type B or T/NK cells)</li><li class="elsevierStyleListItem" id="lsti0545">-Classic Hodgkin lymphoma-type PTLD</li></ul></li></ul>" "etiqueta" => "Appendix 1" "titulo" => "WHO Classification of Lymphoid Neoplasms" "identificador" => "sec0310" ] 1 => array:4 [ "apendice" => "Stage I. Involvement of a single lymph node region, or of a single lymphoid structure (thymus, spleen, Waldeyer's ring) or of an extralymphatic area (Stage I–E). Stage II. Involvement of two or more nodal regions or of nodal and extranodal regions contiguous to the first (E), but always on the same side of the diaphragm. Stage III. Involvement of lymphatic regions or structures on both sides of the diaphragm. There may be contiguous extranodal involvement (E). Stage IV. Disseminated involvement of one or more extralymphatic organs. There may or may not be lymph node involvement. Voluminous mass criterion. Nodal mass greater than 10cm or mediastinal mass equal to or greater than 1/3 of the thoracic diameter (at the level of D5–D6). B symptoms. Fever, night sweats or weight loss (more than 10% in six months)." "etiqueta" => "Appendix 2" "titulo" => "Staging of lymphomas according to Ann Arbor/Cotswolds" "identificador" => "sec0315" ] 2 => array:4 [ "apendice" => "Limited stages Stage I<ul class="elsevierStyleList" id="lis0075"><li class="elsevierStyleListItem" id="lsti0550">-Involvement of a lymph node or several adjacent lymph nodes or</li><li class="elsevierStyleListItem" id="lsti0555">-Single extranodal involvement without lymph node involvement</li></ul> Stage II<ul class="elsevierStyleList" id="lis0080"><li class="elsevierStyleListItem" id="lsti0560">-Involvement of one or more nodal groups on one side of the diaphragm or</li><li class="elsevierStyleListItem" id="lsti0565">-Stage I or II by lymph node involvement, with extranodal extension by contiguity</li><li class="elsevierStyleListItem" id="lsti0570">-Stage II with bulky mass</li><li class="elsevierStyleListItem" id="lsti0575">-Stage I or II with criterion of voluminous mass</li></ul> Advanced stages Stage III<ul class="elsevierStyleList" id="lis0085"><li class="elsevierStyleListItem" id="lsti0580">-Lymph node involvement on both sides of the diaphragm or</li><li class="elsevierStyleListItem" id="lsti0585">-Supradiaphragmatic lymph node involvement plus splenic involvement</li></ul> Stage IV<ul class="elsevierStyleList" id="lis0090"><li class="elsevierStyleListItem" id="lsti0590">-Non-contiguous extranodal involvement</li></ul>" "etiqueta" => "Appendix 3" "titulo" => "Staging of lymphomas according to the Lugano classification" "identificador" => "sec0320" ] ] ] ] "multimedia" => array:8 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Strength of recommendation \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Solid, it must be offered in all situations \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate, it should be offered regularly \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Optional \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">It should generally NOT be offered \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">E \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">It should never be offered \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1805597.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Quality of the findings on which the recommendation is based \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">At least one randomized trial with clinical assessment criteria \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Non-randomized clinical trials \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Expert opinion \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1805603.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical practice classification of the United States Public Health Service/Infectious Diseases Society of America (USPHS/IDSA)." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "CMV: cytomegalovirus; CSF: cerebrospinal fluid; LDH: lactate dehydrogenase; PET: positron emission tomography; MRI: magnetic resonance imaging; CT: computed tomography; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History-taking (Anamnesis) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B Signs (any of the following) Fever Night sweats Weight loss greater than 10% in the last 6 months \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Physical examination \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Palpable lymphadenopathies (number, size and site) Hepatomegaly and splenomegaly Palpable or visible masses or nodules Waldeyer's Ring examination \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lab tests \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hematimetry Biochemical tests with determination of LDH, β-2 microglobulin, transaminases, bilirubin, calcium, uric acid, serum proteins, immunoglobulins and immunofixation Serologies: VHB, HCV, CMV, EBV, Toxoplasma and varicella-zoster Plasma viral load of HIV T-lymphocytes subpopulations (CD4+ and CD8+) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Histology and cytology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Biopsy and bone marrow aspirate<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> CSF cytocentrifugation test (conventional cytology and flow cytometry) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Imaging techniques \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chest X-ray Full-body PET-CT Occasionally: ultrasound, MRI, endoscopy or other imaging studies depending on the site of the lymphoma \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1805600.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "The usefulness of bone marrow biopsy is under discussion in many cases, as PET shows greater sensitivity in the detection of spinal cord involvement. Currently, Hodgkin's lymphoma is only performed in cases of high suspicion of infiltration and negative PET, including peripheral cytopenia." ] ] ] "descripcion" => array:1 [ "en" => "Diagnosis of extension of systemic NHL in HIV-infected patients." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Variables</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Age (<60 years versus ≥60 years)</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Ann Arbor Stage (I–II versus III–IV)</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Number of affected extranodal areas (0–1 versus ≥2)</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Functional capacity according to ECOG score (1–2 versus ≥2) (ECOG assessment: 0: normal activity, 1: symptomatic, but with normal activity, 2: in bed less than 50% of the time, 3: in bed more than 50% of the time, 4: bed-bound 100% of the time)</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Serum LDH (normal versus elevated)</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Risk groups</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Assigning a score 0–1 to each variable of those described, 4 risk groups are defined:</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Low risk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IPI=0–1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Intermediate/low risk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IPI=2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Intermediate/high risk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IPI=3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">High risk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IPI=4–5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1805604.png" ] ] ] ] "descripcion" => array:1 [ "en" => "International Prognostic Index (IPI) for diffuse large B-cell lymphomas." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Gy: grays; IMRT: intensity modulated radiotherapy; ISRT: involved site radiotherapy; BL: Burkitt's lymphoma; DLBCL: diffuse large cell B lymphoma; CT: chemotherapy; RT: radiotherapy." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic non-Hodgkin's lymphomas \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Adjuvant RT after CT stages I and II \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lymphoma where indicated: DLBCL and BL if there is no response to CT, plasmablastic lymphoma in residual masses \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Volume: affected lymph node areas (ISRT) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total doses: 36–40Gy in fractions of 2Gy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Evidence class: IA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Primary central nervous system lymphoma \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Volume: holocranial 45Gy in 25 fractions of 1.8Gy without boost with conventional 3D techniques or using IMRT to avoid irradiation of the hippocampi \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Evidence class IA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Eye involvement: irradiate the entire orbit, better with stereotactic techniques. Lower doses of 31Gy reduce the possibility of brain control \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Evidence class: IIB \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hodgkin's lymphoma \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Favourable disease (EIA, IIA with less than 3 lymph node areas affected), RT 20Gy in 10 fractions \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Favourable disease IIA without bulky disease, but <4 affected lymph node areas: ISRT 30Gy in 15 fractions \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Unfavourable disease with poor response to CT: ISRT dose of 36–40Gy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Evidence class: IA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Palliative radiotherapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Indications: in all cases in which there is uncontrolled pain, compression of adjacent structures, spinal cord compression, bleeding or lack of effectiveness of CT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dosage 30Gy, 10 fractions of 3Gy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Evidence class: IA \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1805605.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Treatment with radiotherapy in patients with lymphoma associated with HIV infection." ] ] 4 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "BURKIMAB: rituximab, methotrexate, dexamethasone, ifosfamide, vincristine, etoposide, cytarabine, doxorubicin and vindesine; CODOX-M: cyclophosphamide, adriamycin, vincristine and methotrexate; CVAD: hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone; EPOCH: etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride; G-CSF: granulocyte colony stimulation factor; IVAC: ifosfamide, etoposide and cytarabine; BL: Burkitt's lymphoma; R-CHOP: rituximab-cyclophosphamide, adriamycin, vincristine and prednisone; RT: radiotherapy; cART: combination antiretroviral treatment; HIV: human immunodeficiency virus." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antitumor treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diffuse large B-cell lymphoma \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IA and IIA: R-CHOP (3 cycles) administered every 21 days+ISRT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other stages: 6 cycles of R-CHOP administered every 21 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Burkitt's syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CODOX-M/IVAC or similar regimens (HyperCVAD or BURKIMAB) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Add rituximab to all previous regimens \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">In patients with significant comorbidity EPOCH can be used \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aggressive B-cell disease with MYC and BCL2 and/or BCL6 gene rearrangement \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chemotherapy regimens designed for BL, with rituximab. AD-EPOCH-R can be used as an alternative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiretroviral treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">If the patient is receiving cART, keep it adapted to the treatment of the lymphoma \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">If the patient is without cART, initiate it together with the lymphoma treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Support and complementary treatment in all cases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tumour lysis syndrome prophylaxis (1st cycle) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Meningeal prophylaxis (see text) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Opportunistic infections prophylaxis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Use of G-CSF \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1805601.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Overview of the treatment of non-Hodgkin's lymphomas associated with HIV infection." ] ] 5 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at6" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "This system includes 7 factors, each of which reduces the probability of disease control at 5 years (see text)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age over 45 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male sex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin<4mg/dl \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Haemoglobin≪10.5g/l \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Leukocytes>1.5×109/l \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lymphocytes≪0.6×109/l \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IV \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1805599.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Hasenclever Prognostic Index for Advanced Hodgkin Disease." ] ] 6 => array:8 [ "identificador" => "tbl0035" "etiqueta" => "Table 7" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at7" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ABVD: adriamycin, bleomycin, vinblastine, dacarbazine; BEACOPP: bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; ESHAP: etoposide, methylprednisolone, cytarabine, cisplatin; ICE: ifosfamide, etoposide, carboplatin; HL: Hodgkin's lymphoma; PET: positron emission tomography; HSCT: hematopoietic stem cell transplantation; HIV: human immunodeficiency virus." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Initial stages with good prognosis criteria \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABVD chemotherapy×2+radiotherapy (see below) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">As an alternative, ABVD chemotherapy×4 (control with PET during treatment) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Initial stages with poor prognosis criteria \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABVD chemotherapy×4+Radiotherapy (see below) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alternatives \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABVD chemotherapy×6 (control with PET during treatment) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chemotherapy BEACOPP×2+ABVD×2+Radiotherapy (see below) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Advanced stages \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABVD chemotherapy×6 and consider radiotherapy on residual masses \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alternative: BEACOPP chemotherapy×6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Relapse of HL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Second line chemotherapy: ESHAP, DHAP, ICE and consolidation with autologous HSCT (exceptionally allogeneic HSCT) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">In patients with refractory or relapse HL after autologous HSCT: brentuximab, PD-1/PDL-1 inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1805598.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Practical recommendations for the treatment of Hodgkin's lymphoma in HIV-infected population." ] ] 7 => array:8 [ "identificador" => "tbl0040" "etiqueta" => "Table 8" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at8" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "HL: Hodgkin's lymphoma; NHL: non-Hodgkin's lymphomas; CR: complete remission; cART: potent combination antiretroviral treatment; HIV: human immunodeficiency virus." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inclusion criteria (all three must be met)<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a>,<a class="elsevierStyleCrossRef" href="#tblfn0015">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1. NHL or HL in any of the following situations \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">After the second CR \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">After the first CR when more than one line of chemotherapy was required \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">After partial remission of the lymphoma when the tumour is considered sensitive to chemotherapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2. Good general condition \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Without active AIDS-defining infection \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Absence of serious diseases (e.g., liver cirrhosis, advanced heart disease) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3. Good control of HIV infection with cART \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">It should not be offered to patients in situation of virologic failure without rescue option \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Therapeutic procedure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Administration of high doses of chemotherapy, followed by the infusion of hematopoietic stem cells obtained from peripheral blood of the same patient \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1805602.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "The joint opinion of haematologists or oncologists and specialists in HIV infection is required." ] 1 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "b" "nota" => "The informed consent of the patient is required." ] ] ] "descripcion" => array:1 [ "en" => "Autologous transplants of hematopoietic stem cell in patients with lymphomas and HIV infection." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:186 [ 0 => array:3 [ "identificador" => "bib0935" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:1 [ …1] ] ] ] ] 1 => array:3 [ "identificador" => "bib0940" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:1 [ …1] ] ] ] ] 2 => array:3 [ "identificador" => "bib0945" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 3 => array:3 [ "identificador" => "bib0950" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 4 => array:3 [ "identificador" => "bib0955" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 5 => array:3 [ "identificador" => "bib0960" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 6 => array:3 [ "identificador" => "bib0965" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 7 => array:3 [ "identificador" => "bib0970" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 8 => array:3 [ "identificador" => "bib0975" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:1 [ …1] ] ] ] ] 9 => array:3 [ "identificador" => "bib0980" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 10 => array:3 [ "identificador" => "bib0985" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:1 [ …1] ] ] ] ] 11 => array:3 [ "identificador" => "bib0990" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 12 => array:3 [ "identificador" => "bib0995" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:1 [ …1] ] ] ] ] 13 => array:3 [ "identificador" => "bib1000" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 14 => array:3 [ "identificador" => "bib1005" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:1 [ …1] ] ] ] ] 15 => array:3 [ "identificador" => "bib1010" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 16 => array:3 [ "identificador" => "bib1015" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 17 => array:3 [ "identificador" => "bib1020" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 18 => array:3 [ "identificador" => "bib1025" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:1 [ …1] ] ] ] ] 19 => array:3 [ "identificador" => "bib1030" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:1 [ …1] ] ] ] ] 20 => array:3 [ "identificador" => "bib1035" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 21 => array:3 [ "identificador" => "bib1040" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:1 [ …1] ] ] ] ] 22 => array:3 [ "identificador" => "bib1045" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 23 => array:3 [ "identificador" => "bib1050" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 24 => array:3 [ "identificador" => "bib1055" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 25 => array:3 [ "identificador" => "bib1060" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 26 => array:3 [ "identificador" => "bib1065" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 27 => array:3 [ "identificador" => "bib1070" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 28 => array:3 [ "identificador" => "bib1075" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 29 => array:3 [ "identificador" => "bib1080" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 30 => array:3 [ "identificador" => "bib1085" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 31 => array:3 [ "identificador" => "bib1090" "etiqueta" => "32" "referencia" => array:1 [ 0 => 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array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 111 => array:3 [ "identificador" => "bib1490" "etiqueta" => "112" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 112 => array:3 [ "identificador" => "bib1495" "etiqueta" => "113" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] 113 => array:3 [ "identificador" => "bib1500" "etiqueta" => "114" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Panel de expertos de GeSIDA y Plan Nacional sobre el Sida. Documento de consenso de GeSIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en adultos infecta- dos por el virus de la inmunodeficiencia humana. 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"vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015100000001/v1_201807170422/S2387020618302055/v1_201807170422/en/main.assets" "Apartado" => array:4 [ "identificador" => "46796" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Consensus statement" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015100000001/v1_201807170422/S2387020618302055/v1_201807170422/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618302055?idApp=UINPBA00004N"]

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Consensus statement

GESIDA/PETHEMA recommendations on the diagnosis and treatment of lymphomas in patients infected by the human immunodeficiency virus

Recomendaciones de GESIDA/PETHEMA sobre el diagnóstico y tratamiento de los linfomas en pacientes infectados por el virus de la inmunodeficiencia humana

Pilar Mirallesa,

Corresponding author

pilarmirallesm@gmail.com

Corresponding author.

, José Tomás Navarrob, Juan Berenguera, José Gómez Codinac, Mi Kwona, David Serranoa, José Luis Díez-Martína, Salvador Villàb, Rafael Rubiod, Javier Menárgueza, José-María Ribera Santasusanab

a Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain

b Institut Català d’Oncologia, Hospital Universitari Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autónoma de Barcelona, Badalona, Barcelona, Spain

c Hospital La Fe, Valencia, Spain

d Hospital 12 de Octubre, Madrid, Spain

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in 1996 radically changed the natural history of HIV infection and drastically reduced the incidence of tumours such as PCNSL&#44; which occur with very low CD4&#43; T lymphocyte counts&#46;<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">2</span></a> After the introduction of cART&#44; lymphomas that usually occur with higher CD4&#43; T lymphocyte counts&#44; such as Burkitt&#39;s lymphoma &#40;BL&#41; and HL also decreased&#44; but not as significantly&#46;<a class="elsevierStyleCrossRefs" href="#bib0945"><span class="elsevierStyleSup">3&#44;4</span></a> In addition&#44; the use of cART has been decisive in the improvement of the prognosis of these tumours&#46;<a class="elsevierStyleCrossRefs" href="#bib0940"><span class="elsevierStyleSup">2&#44;5&#8211;8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">This document updates the recommendations on the diagnosis and treatment of lymphomas in HIV-infected patients published in 2008 by a panel of experts from the AIDS Study Group &#40;GESIDA&#41; and the Spanish Program for Haematology Treatments PETHEMA&#46;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">9</span></a> As in the previous edition&#44; these recommendations are accompanied by a categorization of the level of scientific evidence following the classification scheme for clinical practice of the <span class="elsevierStyleItalic">United States Public Health Service</span> and the <span class="elsevierStyleItalic">Infectious Diseases Society of America</span> &#40;USPHS&#47;IDSA&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Systemic non-Hodgkin&#39;s lymphomas</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Histopathology and classification</span><p id="par0020" class="elsevierStylePara elsevierViewall">The variety or histological subtype is the most important variable to predict clinical behaviour and to establish the prognosis of lymphomas&#46; The WHO classification continues to be the accepted standard for terminology and classification of lymphoid neoplasms&#46; Some changes were introduced in the latest edition of this classification&#44; which is an update of the one published in 2008&#44; including the subdivision of diffuse large B-cell lymphomas &#40;DLBCL&#41; depending on its germinal centre or non-germinal centre origin<a class="elsevierStyleCrossRef" href="#bib0980"><span class="elsevierStyleSup">10</span></a> &#40;<a class="elsevierStyleCrossRef" href="#sec0310">Appendix 1</a>&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">NHL associated with HIV infection are mainly of B-lineage&#44; in particular DLBCL &#40;73&#37;&#41; and less frequently BL &#40;19&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0955"><span class="elsevierStyleSup">5</span></a> There are rare varieties but strongly linked to HIV infection&#44; such as plasmablastic lymphoma and other related to type 8 human herpes virus &#40;HHV-8&#41;&#44; such as primary effusion lymphoma and multicentric Castleman&#39;s disease &#40;MCD&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Diagnosis and extension study</span><p id="par0030" class="elsevierStylePara elsevierViewall">Systemic NHL associated with HIV infection usually occur in young men with CD4&#43; lymphocyte values &#60;200&#47;mm<span class="elsevierStyleSup">3</span>&#44; frequently being an AIDS-defining disease&#46; The tumour is usually in advanced stages and is often accompanied by B symptoms and extranodal involvement&#44; particularly of the bone marrow&#46; There may also be central nervous system &#40;CNS&#41; involvement&#44; both at the onset and during the course of the disease&#46; The leptomeningeal involvement predominates in the initial stages&#44; occurs more frequently when there is bone marrow or otorhinolaryngological area invasion and may be asymptomatic&#46; The involvement of the brain parenchyma in the form of masses is more common in the context of a progressive and refractory lymphoma&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The diagnosis of lymphoma and the identification of the specific subtype require a histological study with immunohistochemistry and sometimes cytogenetic and molecular studies&#46; 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but the Ann Arbor&#47;Cotswolds staging system has traditionally been used&#44;<a class="elsevierStyleCrossRefs" href="#bib0995"><span class="elsevierStyleSup">13&#44;14</span></a> which was designed for HL &#40;<a class="elsevierStyleCrossRef" href="#sec0315">Appendix 2</a>&#41;&#46; A new&#44; more specific system for NHLs &#40;the Lugano classification&#41; derived from the Ann Arbor&#47;Cotswolds classification has recently been proposed<a class="elsevierStyleCrossRef" href="#bib0990"><span class="elsevierStyleSup">12</span></a> &#40;<a class="elsevierStyleCrossRef" href="#sec0320">Appendix 3</a>&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Factors related to the prognosis</span><p id="par0050" class="elsevierStylePara elsevierViewall">In patients with HIV infection and NHL and before the introduction of cART&#44; factors related to the prognosis were mainly related to the characteristics of the patients and the viral infection itself&#44; 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Age-adjusted IPI is a simplified model for younger populations that classifies patients according to age &#40;&#8804;60 or &#62;60years&#41;&#44; stage&#44; general condition and serum LDH&#46;<a class="elsevierStyleCrossRef" href="#bib1035"><span class="elsevierStyleSup">21</span></a> Both the IPI and the age-adjusted IPI have shown prognostic value in patients with HIV infection and NHL&#46;<a class="elsevierStyleCrossRefs" href="#bib0955"><span class="elsevierStyleSup">5&#44;17&#8211;20</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Treatment</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Diffuse large B-cell lymphoma</span><p id="par0060" class="elsevierStylePara elsevierViewall">In patients without HIV infection&#44; DLBCL is a potentially curable disease whose treatment depends on the stage of the tumour&#46; For localized stages&#44; chemotherapy combined with immunotherapy targeting the CD20 antigen and radiotherapy of the affected area is used&#46; Advanced stages are treated with the combination of chemotherapy and immunotherapy&#46; The adequate control of HIV infection with cART and the use of hematopoietic growth factors have made it possible for patients with HIV and lymphoma to receive the same chemotherapy regimens as patients without HIV infection&#44; with comparable clinical results&#46;<a class="elsevierStyleCrossRefs" href="#bib1040"><span class="elsevierStyleSup">22&#8211;24</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The most commonly used first-line polychemotherapy regimen for DLBCL is CHOP &#40;cyclophosphamide&#44; adriamycin&#44; vincristine and prednisone&#41; with anti-CD20 &#40;R-CHOP&#41;&#44; with whom complete remission &#40;CR&#41; is obtained in 60&#8211;80&#37; of patients with NHL in stages II to IV&#46; There are few data showing that 8 cycles are more effective than 6&#44; therefore&#44; 6 cycles are usually administered with a 21 day interval between each one&#46; It is very important to administer the appropriate doses of cytostatics and to adjust to the intervals&#44; since the reductions in drug-dose intensity&#44; particularly adriamycin and cyclophosphamide&#44; decrease the percentage of CR&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In patients with HIV infection&#44; two phase II studies have been published with R-CHOP in which the percentages of CRs were 69 and 77&#37;&#44; with an overall survival &#40;OS&#41; at 2 and 3 years of 75 and 56&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib1055"><span class="elsevierStyleSup">25&#44;26</span></a> Although some studies have shown better results with infusion regimens such as R-EPOCH compared to historical controls treated with R-CHOP&#44;<a class="elsevierStyleCrossRefs" href="#bib1065"><span class="elsevierStyleSup">27&#8211;29</span></a> no regimen has surpassed R-CHOP in randomized clinical trials&#44; so the latter is considered the standard regimen in our environment&#46;<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">30</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In patients with HIV infection and NHL&#44; the addition of rituximab to chemotherapy is safe and recommendable&#44; although there is some hesitation in highly-immunocompromised patients due to the results of a phase III clinical trial published in 2005&#44; where R-CHOP was compared to CHOP&#44; in which mortality was higher due to infection in the R-CHOP arm in patients with CD4&#43; T lymphocyte values &#60;50&#47;mm<span class="elsevierStyleSup">3</span>&#46;<a class="elsevierStyleCrossRef" href="#bib1085"><span class="elsevierStyleSup">31</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Treatment with radiotherapy in patients with lymphoma associated with HIV infection does not differ substantially from that indicated in the general population&#44;<a class="elsevierStyleCrossRef" href="#bib1090"><span class="elsevierStyleSup">32</span></a> and as such it plays a secondary role in the treatment of NHL&#44; having a more decisive role in the treatment of HL &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; Adjuvant radiotherapy on the affected area in patients with NHL in localized stages &#40;IA and IIA&#41; is indicated after completing 3 cycles of chemotherapy&#46; In bulky mass lymphomas&#44; radiation therapy can be administered to the mass after chemotherapy is complete&#46; Treatment with radiotherapy can also be used for palliative purposes in cases of uncontrolled pain&#44; compression of adjacent structures&#44; spinal cord compression&#44; bleeding or lack of chemotherapy effectiveness&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Aggressive B-cell lymphoma with <span class="elsevierStyleItalic">MYC</span> and <span class="elsevierStyleItalic">BCL2</span> and&#47;or <span class="elsevierStyleItalic">BCL6</span> gene rearrangement</span><p id="par0085" class="elsevierStylePara elsevierViewall">In 5&#8211;10&#37; of the DLBCL there is a rearrangement of the gene <span class="elsevierStyleItalic">MYC</span>&#44; which is often associated with translocations of the gene <span class="elsevierStyleItalic">BCL2</span> and&#47;or the <span class="elsevierStyleItalic">BCL6</span>&#46; These NHL are considered as a separate category in the new WHO classification due to their extraordinary aggressiveness&#44; poor response to standard treatments and poor prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0980"><span class="elsevierStyleSup">10&#44;33&#44;34</span></a> They have also been called <span class="elsevierStyleItalic">double hit</span> &#40;DH&#41; or <span class="elsevierStyleItalic">triple hit</span> &#40;TH&#41;&#44; according to the presence of two or three translocations&#46; What the best treatment for DH or TH NHL is still unknown&#44; but it is known that their response is worse in the case of R-CHOP than DLBCL&#44; with CR percentages of 40&#37;&#44; OS at 2 years of 35&#8211;41&#37; and OS at 5 years of 25&#8211;30&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib1105"><span class="elsevierStyleSup">35&#8211;37</span></a> The intensive chemotherapy regimens used to treat BL have been used with these lymphomas&#44; with slightly better outcomes than those obtained with R-CHOP&#46;<a class="elsevierStyleCrossRefs" href="#bib1120"><span class="elsevierStyleSup">38&#44;39</span></a> The AD-EPOCH-R regimen &#40;<span class="elsevierStyleItalic">dose-adjusted</span> EPOCH-rituximab&#41; has shown promising results and could be used in HIV-infected patients with this type of lymphoma&#46;<a class="elsevierStyleCrossRefs" href="#bib1120"><span class="elsevierStyleSup">38&#44;40&#44;41</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Burkitt&#39;s lymphoma</span><p id="par0090" class="elsevierStylePara elsevierViewall">This lymphoma is characterized by the deregulation of the <span class="elsevierStyleItalic">MYC</span> oncogene and for its great aggressiveness&#46; In patients with HIV infection&#44; BL usually occurs in patients without previous diagnosis of AIDS and with a relatively preserved immune system&#46; Despite this&#44; the regimens used for the DLBCL have had very poor results in the BL&#44; as it happens in the population not infected with HIV&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The best results against BL have been obtained with multidrug chemotherapy regimens with cytostatics without cross resistance and good penetration in the CNS together with intrathecal prophylaxis&#46; In fact&#44; in patients with BL without HIV infection&#44; the cyclophosphamide&#44; adriamycin&#44; vincristine and methotrexate regimen &#40;CODOX-M&#41; alternating with ifosfamide&#44; etoposide and cytarabine &#40;IVAC&#41; has achieved CR in 90&#37; of patients with event-free survival &#40;EFS&#41; at 2 years in 50&#8211;70&#37; of cases&#46;<a class="elsevierStyleCrossRefs" href="#bib1140"><span class="elsevierStyleSup">42&#8211;44</span></a> Good therapeutic results have also been obtained in BL with hyperfractionated cyclophosphamide&#44; vincristine&#44; doxorubicin and dexamethasone &#40;Hyper-CVAD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1155"><span class="elsevierStyleSup">45</span></a> Experience with Hyper-CVAD and CODOX-M&#47;IVAC for the treatment of BL in patients with HIV is not extensive&#44; but published studies show a CR in 64&#8211;92&#37; of cases&#44; survival at 2 years from 47 to 59&#37; and a toxicity similar to that of patients without HIV infection&#46;<a class="elsevierStyleCrossRefs" href="#bib1160"><span class="elsevierStyleSup">46&#8211;49</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Some clinical trials in patients without HIV infection indicate that the addition of rituximab to these intensive chemotherapy regimens improves efficacy without significantly increasing toxicity&#46;<a class="elsevierStyleCrossRefs" href="#bib1180"><span class="elsevierStyleSup">50&#44;51</span></a> Also in patients with HIV infection and BL&#44; intensive chemotherapy regimens with rituximab have been studied&#44; such as the B-ALL&#47;NHL2002 protocol of the German multicentre adult acute lymphoblastic leukaemia &#40;GMALL&#41; study group and its Spanish variant Burkimab&#44; with which CR has been achieved in more than 80&#37; of cases&#44; with an 11&#37; mortality in induction and a higher incidence of infections than in HIV negative patients treated with the same protocol&#46;<a class="elsevierStyleCrossRefs" href="#bib1190"><span class="elsevierStyleSup">52&#44;53</span></a> On the other hand&#44; in the <span class="elsevierStyleItalic">AIDS Malignancy Consortium 048</span> trial&#44; the addition of rituximab to the modified CODOX-M&#47;IVAC regimen has achieved a first-year OS of 72&#37; with a toxicity similar to that of individuals without HIV infection&#46;<a class="elsevierStyleCrossRef" href="#bib1200"><span class="elsevierStyleSup">54</span></a> The R-EPOCH regimen has also been evaluated in BL in a prospective study with 30 patients without CNS involvement&#44; 11 of whom were infected with HIV<a class="elsevierStyleCrossRef" href="#bib1205"><span class="elsevierStyleSup">55</span></a>&#59; after a median follow-up of 73 months 100&#37; of the patients were alive and 90&#37; free of progression&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">It is important to note that patients with BL should be treated by teams with experience in the management of this type of lymphomas&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Plasmablastic lymphoma</span><p id="par0115" class="elsevierStylePara elsevierViewall">Plasmablastic lymphoma is a very aggressive and infrequent lymphoma that is considered a different entity from the DLBCL and that mainly affects HIV-infected population&#46;<a class="elsevierStyleCrossRef" href="#bib1210"><span class="elsevierStyleSup">56</span></a> Initially&#44; cases with involvement of the oral cavity were described&#44;<a class="elsevierStyleCrossRef" href="#bib1215"><span class="elsevierStyleSup">57</span></a> but its appearance has been later described in other locations&#46;<a class="elsevierStyleCrossRef" href="#bib1220"><span class="elsevierStyleSup">58</span></a> The prognosis&#44; even in the era of cART&#44; is very poor&#44; with a median survival of less than one year&#46;<a class="elsevierStyleCrossRef" href="#bib1220"><span class="elsevierStyleSup">58</span></a> Intensive chemotherapy regimens have not shown better results than CHOP&#44; so there is currently no standard treatment for this type of NHL&#46; If the patient&#39;s condition permits&#44; a consolidation with an autologous hematopoietic stem cell transplant &#40;HSCT&#41; is generally recommended&#44; as well as intrathecal prophylaxis&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Recently&#44; drugs used for the treatment of multiple myeloma have been studied&#44; given the plasmocytic differentiation of plasmablastic lymphoma&#46; The most used has been bortezomib&#44; a proteasome inhibitor that has been used alone or in combination with chemotherapy&#44; both as a salvage therapy and as a first-line treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib1225"><span class="elsevierStyleSup">59&#44;60</span></a> Recently&#44; the outcome of the plasmablastic lymphoma treatment with bortezomib and EPOCH in 3 patients have been reported&#44; all of whom achieved CR with survival between 12 and 24 months at the time of publication&#46;<a class="elsevierStyleCrossRef" href="#bib1235"><span class="elsevierStyleSup">61</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Primary effusion lymphoma</span><p id="par0125" class="elsevierStylePara elsevierViewall">Primary effusion lymphoma is an uncommon variety of NHL associated with HIV infection that frequently occurs along with Kaposi&#39;s sarcoma &#40;KS&#41;&#46; HHV-8 plays a key role in the pathogenesis of both tumour&#44;<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">62</span></a> DNA virus that infects mainly lymphoblastic cells&#44; producing a state of latent infection&#46; Primary effusion lymphoma typically originates in some of the serous cavities such as pleura&#44; pericardium or peritoneum&#44; so that the clinical manifestations depend on the cavity in which the tumour originates&#46; Tumour masses are rarely developed&#44; although lymphoma can spread through serosa surfaces&#46;<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">62</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The diagnosis is made by cytological fluid examination&#46; The key diagnostic criterion for primary effusion lymphoma is the presence of HHV-8 in the nuclei of the malignant cells&#44; which is demonstrated by positive immunohistochemical staining for the nuclear antigen 1 associated with latency &#40;LANA-1&#41;&#46; Despite the frequent co-infection with EBV&#44; the latency membrane protein &#40;LMP1&#41; staining is negative&#46; The general lymphoma staging system &#40;IPI&#41; is not useful for primary effusion lymphoma&#44; which&#44; by definition&#44; is in stage IV&#46; However&#44; an extension study is recommended through Positron Emission Tomography &#40;PET&#41; &#8211; Thoracic&#44; abdominal and pelvic computed tomography &#40;CT&#41;&#46; It is often necessary to perform cardiac ultrasound&#44; bone marrow biopsy or lumbar puncture within the initial extension study&#46; In a series with 28 cases&#44; the absence of cART at the time of diagnosis and the poor general state of the patient were identified as the main factors of poor prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib1245"><span class="elsevierStyleSup">63</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">There is no standardized treatment for primary effusion lymphoma&#46; Isolated cases have been described in which CR with CHOP and cART was achieved&#46;<a class="elsevierStyleCrossRefs" href="#bib1250"><span class="elsevierStyleSup">64&#44;65</span></a> However&#44; in a single-centre series with 11 cases treated with CHOP and cART&#44; CR was obtained in 42&#37;&#44; with a median survival of 6 months&#46;<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">66</span></a> There is very little experience with EPOCH<a class="elsevierStyleCrossRef" href="#bib1265"><span class="elsevierStyleSup">67</span></a> and also with autologous HSCT<a class="elsevierStyleCrossRefs" href="#bib1270"><span class="elsevierStyleSup">68&#44;69</span></a> or allogeneic HSCT&#44;<a class="elsevierStyleCrossRef" href="#bib1280"><span class="elsevierStyleSup">70</span></a> with results still inconclusive&#46; However&#44; given the poor prognosis of this tumour&#44; HSCT is a therapeutic option that should be considered in appropriately selected patients&#46; Bortezomib has in vitro activity against primary effusion lymphoma<a class="elsevierStyleCrossRef" href="#bib1285"><span class="elsevierStyleSup">71</span></a> and a phase II clinical trial is currently underway of bortezomib associated with chemotherapy for the treatment of this lymphoma&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Multicentric Castleman&#39;s disease</span><p id="par0140" class="elsevierStylePara elsevierViewall">MCD is an aggressive lymphoproliferative process that occurs more frequently in HIV-infected patients than in the general population&#46; Although not considered a lymphoma&#44; patients with MCD&#44; especially those infected with HIV&#44; are at risk of progression to NHL&#46;<a class="elsevierStyleCrossRef" href="#bib1290"><span class="elsevierStyleSup">72</span></a> There are two histological variants of MCD&#58; the hyalinovascular and the plasmocellular&#46; The latter is the one usually present in HIV-infected patients&#46; In these patients&#44; the incidence of MCD has increased since the introduction of cART and an association with CD4&#43; T lymphocyte values or with the administration of cART has not been demonstrated&#46;<a class="elsevierStyleCrossRef" href="#bib1295"><span class="elsevierStyleSup">73</span></a> The etiopathogenesis of this entity is not well known&#44; but the available information indicates that HHV-8 plays a key role&#44; since high levels of HHV-8 DNA have been found in peripheral blood mononuclear cells as well as in the plasma of MCD patients&#46;<a class="elsevierStyleCrossRefs" href="#bib1300"><span class="elsevierStyleSup">74&#44;75</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">MCD typically presents with fever&#44; sweating and constitutional symptoms&#46; On physical examination&#44; there are usually enlarged lymph nodes and sometimes hepatomegaly and&#47;or splenomegaly&#46; In addition&#44; the coexistence of KS is common in patients with HIV infection and MCD&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">There are hardly any therapeutic clinical trials on MCD and most of the information in this regard comes from clinical cases or series with few patients&#46; In the MCD associated with HIV&#44; treatment with rituximab has achieved remissions in 67&#8211;71&#37; of patients&#44; with survival at 2 years of 90&#8211;95&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib1310"><span class="elsevierStyleSup">76&#44;77</span></a> It is important to note that in patients with HIV infection and MCD&#44; treatment with rituximab has been associated with a reduction in the risk of developing NHL&#44;<a class="elsevierStyleCrossRef" href="#bib1320"><span class="elsevierStyleSup">78</span></a> although it may favour the occurrence of KS&#46; The usual regimen consists of 4 375<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> doses of rituximab at one-week intervals&#46; However&#44; in severe cases&#44; the combination of rituximab with chemotherapy such as CHOP or etoposide should be considered &#40;100<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>4 weeks&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1090"><span class="elsevierStyleSup">32&#44;79</span></a> Given that the symptomatology of the MCD seems to be related to high plasma levels of interleukin-6 &#40;IL-6&#41;&#44; monoclonal antibodies against this cytokine &#40;siltuximab&#41; or its receptor &#40;tocilizumab&#41; have been used&#44; which has been effective in HIV-negative patients&#46;<a class="elsevierStyleCrossRefs" href="#bib1330"><span class="elsevierStyleSup">80&#44;81</span></a> However&#44; the experience in HIV-positive patients is very limited&#46; HHV-8 is sensitive in vitro to different antivirals such as ganciclovir&#44; foscarnet and cidofovir&#44;<a class="elsevierStyleCrossRef" href="#bib1340"><span class="elsevierStyleSup">82</span></a> and series with few HIV-infected and MCD patients have been published in which treatment with ganciclovir<a class="elsevierStyleCrossRef" href="#bib1345"><span class="elsevierStyleSup">83</span></a> or valganciclovir<a class="elsevierStyleCrossRef" href="#bib1350"><span class="elsevierStyleSup">84</span></a> has been associated with decreased HHV-8 viraemia and clinical improvement&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Lymphomatous meningitis</span><p id="par0155" class="elsevierStylePara elsevierViewall">The prevalence of CNS involvement in HIV-associated NHL at the time of diagnosis is 5&#8211;15&#37; and the typical form is lymphomatous meningitis &#40;LM&#41;&#46; In the population in question&#44; as in patients without HIV infection&#44; the frequency of LM varies according to the type of NHL and is more common in the BL &#40;25&#8211;30&#37;&#41; than in DLBCL &#40;5&#8211;10&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1355"><span class="elsevierStyleSup">85&#44;86</span></a> In one study&#44; the frequency of secondary CNS involvement was lower in patients receiving cART before NHL than in patients not receiving cART&#46;<a class="elsevierStyleCrossRef" href="#bib1365"><span class="elsevierStyleSup">87</span></a></p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Diagnosis</span><p id="par0160" class="elsevierStylePara elsevierViewall">LM may occur without clinical data of neurological involvement&#44; and for this reason a cerebrospinal fluid &#40;CSF&#41; evaluation should be part of the extension study of aggressive NHL associated with HIV&#46; The study should include glucose and protein quantification&#44; as well as a cellularity study by light microscopy after CSF cytocentrifugation&#44; and by flow cytometry&#46; When these techniques are not conclusive&#44; the study of the rearrangement of the immunoglobulin heavy-chain gene in the CSF may be useful&#46; In one study&#44; the presence of EBV DNA in CSF was associated with an increased risk of CNS involvement by NHL at the time of diagnosis or relapse&#46;<a class="elsevierStyleCrossRef" href="#bib1370"><span class="elsevierStyleSup">88</span></a> Patients with clinical manifestations suggestive of LM should undergo imaging tests&#44; preferably magnetic resonance imaging &#40;MRI&#41; with contrast&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Central nervous system prophylaxis</span><p id="par0165" class="elsevierStylePara elsevierViewall">There are no studies that have evaluated the efficacy and safety of meningeal prophylaxis in patients with NHL and HIV infection&#46; Despite this&#44; this committee considers that it should be carried out in patients with &#8220;high risk&#8221; NHL&#44; such as BL&#44; lymphomas with <span class="elsevierStyleItalic">MYC gene rearrangement</span>&#44; plasmablastic lymphoma and DLBCL with elevated LDH and more than one extranodal site or with invasion of the epidural space&#44; breast&#44; kidney&#44; testicle or bone marrow &#40;AII&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1375"><span class="elsevierStyleSup">89&#8211;91</span></a> There are several prophylaxis regimens&#44; but this consensus group recommends intrathecal &#40;IT&#41; administration of methotrexate &#40;MTX&#41; &#40;12<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; cytosine arabinoside &#40;Ara-C&#41; &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#41; and hydrocortisone &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#41; on day 1 of each cycle &#40;BII&#41;&#46; An alternative to IT prophylaxis is the use of high doses of systemic chemotherapy&#44; usually intravenous MTX with or without IT chemotherapy &#40;CIII&#41;&#46; The available information suggests that in order to achieve adequate levels of MTX in the CSF and brain parenchyma&#44; doses of the drug should be administered intravenously 3<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib1390"><span class="elsevierStyleSup">92</span></a> High doses of intravenous MTX can be administered concurrently with regimens such as R-CHOP or R-CHOP with etoposide &#40;R-CHOEP&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1395"><span class="elsevierStyleSup">93&#44;94</span></a> In patients with HIV infection&#44; administration of high doses of intravenous MTX with R-CHOP could cause delays in subsequent cycles of R-CHOP due to the greater tendency of these patients to suffer from cytopenia with chemotherapy&#44; which could result counterproductive in terms of good systemic disease control&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Treatment</span><p id="par0170" class="elsevierStylePara elsevierViewall">For the treatment of LM&#44; triple IT therapy with MTX &#40;12<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; Ara-C &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#41; and hydrocortisone &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#41; every 3 or 4 days until the disappearance of tumour cells in CSF and then 2 more doses&#44; administering at least 5 doses &#40;BII&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Ara-C in liposomal depot form has a longer half-life and better CNS distribution than conventional Ara-C&#46; It can be administered biweekly&#44; which avoids repeated lumbar punctures and&#44; in some cases&#44; the placement of Ommaya-type reservoirs&#46; The recommended regimen contemplates an induction phase with 50<span class="elsevierStyleHsp" style=""></span>mg biweekly until completing 5 doses&#44; followed by a consolidation and maintenance phase of 50<span class="elsevierStyleHsp" style=""></span>mg once a month until completing 5 doses &#40;BII&#41;&#46; In a study with patients without HIV infection&#44; treatment of LM with liposomal Ara-C was more effective than conventional Ara-C treatment and was associated with better quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib1405"><span class="elsevierStyleSup">95</span></a> There is less information in HIV-infected patients&#44; although the experience in a small series was favourable&#46;<a class="elsevierStyleCrossRef" href="#bib1410"><span class="elsevierStyleSup">96</span></a> The administration of liposomal IT Ara-C can associate neurological toxicity when administered concomitantly with MTX at high doses and Ara-C systemically&#46;<a class="elsevierStyleCrossRef" href="#bib1415"><span class="elsevierStyleSup">97</span></a> For this reason&#44; it is recommended to administer dexamethasone by IT route with each liposomal Ara-C dose and separate its administration from other intravenous cytostatics that cross the blood-brain barrier well by at least 7 days&#44; mainly Ara-C&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Craniospinal radiation therapy is currently not recommended for prophylaxis or treatment of CNS involvement in patients with systemic NHL&#46; First&#44; because there is an effective alternative such as intrathecal and&#47;or systemic chemotherapy&#46; Secondly&#44; because it produces great toxicity&#44; both haematological and non-haematological&#46; Finally&#44; because it is technically complex given that there is a risk of overlapping irradiation volumes on various anatomical regions&#46;</p></span></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Practical recommendations for the treatment of systemic lymphomas in HIV-infected patients</span><p id="par0185" class="elsevierStylePara elsevierViewall">The overview of the treatment of systemic NHL associated with HIV infection is detailed in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Diffuse large B-cell lymphoma</span><p id="par0190" class="elsevierStylePara elsevierViewall">6 cycles of R-CHOP administered every 21 days are recommended &#40;AII&#41;&#44; keeping in mind that patients with CD4&#43; T lymphocytes &#60;50&#47;mm<span class="elsevierStyleSup">3</span> could have more infectious complications&#46; The R-EPOCH-DA infusion regimen may be an alternative&#44; although it has not been shown to be more effective than R-CHOP and is more toxic than the latter &#40;BII&#41;&#46; In patients with stage IA or IIA the recommended treatment is 3 cycles of R-CHOP administered every 21 days followed by radiotherapy over affected area &#40;AIII&#41;&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Burkitt&#39;s lymphoma</span><p id="par0195" class="elsevierStylePara elsevierViewall">Patients with good immunological status and good general condition should receive intensive chemotherapy with regimens such as CODOX-M&#47;IVAC&#44; Hyper-CVAD or a similar protocol as that of the PETHEMA group &#40;Burkimab&#41; designed specifically for this tumour &#40;AII&#41;&#46; In addition&#44; it is recommended to associate rituximab with the chemotherapy regimens &#40;AI&#41;&#46; These intensive regimens should be used by experienced teams&#44; since they carry a toxicity mortality of 7&#8211;10&#37;&#46; Other regimens can be used in patients with significant comorbidity&#44; such as EPOCH &#40;CII&#41;&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Aggressive B-cell lymphoma with <span class="elsevierStyleItalic">MYC</span> and <span class="elsevierStyleItalic">BCL2</span> and&#47;or <span class="elsevierStyleItalic">BCL6</span> gene rearrangement</span><p id="par0200" class="elsevierStylePara elsevierViewall">Given the poor results obtained with the R-CHOP regimen&#44; intensive chemotherapy regimens designed for BL &#40;BII&#41; or the AD-EPOCH-R regimen&#44; which has shown promising results &#40;BII&#41;&#44; can be used&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Plasmablastic lymphoma</span><p id="par0205" class="elsevierStylePara elsevierViewall">There is no good therapeutic option at present for this lymphoma&#46; Intensive regimens such as DA-EPOCH&#44; which have shown greater efficacy than CHOP in few patient series and isolated cases &#40;BII&#41;&#44; can be considered&#46; Chemotherapy such as EPOCH can also be used together with bortezomib&#44; although the available data are limited &#40;BIII&#41;&#46; Autologous HSCT could be considered in patients with rearranged <span class="elsevierStyleItalic">MYC</span> in those that have not reached a complete response &#40;CIII&#41;&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Multicentric Castleman&#39;s disease</span><p id="par0210" class="elsevierStylePara elsevierViewall">It is recommended to administer rituximab&#46; The usual pattern is 4 doses of 375<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> at 1-week intervals &#40;AII&#41;&#46; In the most severe cases&#44; the combination of rituximab with CHOP or etoposide at a dose of 100<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> should be considered &#40;BII&#41;&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Primary effusion lymphoma</span><p id="par0215" class="elsevierStylePara elsevierViewall">There is no standardized treatment for primary effusion lymphoma&#46; The first-line treatment can be performed with CHOP or EPOCH&#46; Comparative studies have not been carried out and there is no standard optimal therapy &#40;AII&#41;&#46; Given the poor prognosis of this tumour&#44; autologous HSCT is a therapeutic option that should be considered in appropriately selected patients &#40;CIII&#41;&#46; Another therapeutic option not yet consolidated is bortezomib associated with chemotherapy &#40;DIII&#41;&#46;</p></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Second-line treatments</span><p id="par0220" class="elsevierStylePara elsevierViewall">There is little information about second-line treatments in HIV-infected patients&#46; It is important to differentiate the treatment of relapsed NHL from the treatment of refractory NHL&#46;</p><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Relapsed systemic lymphoma</span><p id="par0225" class="elsevierStylePara elsevierViewall">Relapses of systemic NHL in HIV-infected patients are a relatively common problem&#46; A relapse was documented in 16&#37; of patients who achieved CR in the collaborative study of GESIDA and PETHEMA of NHL during the era of cART&#46; The relapse occurred a median of 10 months after CR with an interquartile range from 2 to 16 months&#46;<a class="elsevierStyleCrossRef" href="#bib0955"><span class="elsevierStyleSup">5</span></a> Some patients in first relapse achieve a second CR after a second-line treatment&#46; When choosing a second-line treatment&#44; three aspects should be assessed&#58; the quality of life of the patient &#40;general condition and associated diseases&#41;&#44; the previous treatments and the bone marrow reserve&#46; In patients with a good general condition and with HIV infection under control&#44; who have previously received R-CHOP or R-EPOCH&#44; treatment with etoposide&#44; cisplatin&#44; methylprednisolone and cytarabine &#40;ESHAP&#41;&#44; generally combined with rituximab&#44; may be considered&#46;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">98</span></a> In those in which CR or a good partial remission of NHL is achieved after second-line chemotherapy&#44; consolidation with autologous HSCT can be considered&#46; Several patient and case&#8211;control series studies have shown that the results of autologous HSCT are not different from those observed in the non-immunocompromised population&#46;<a class="elsevierStyleCrossRefs" href="#bib1425"><span class="elsevierStyleSup">99&#44;100</span></a> The results with the different treatments offer CR rates around 30&#37;&#44; although survival at one year in patients who achieve CR is around 80&#37;&#44; with or without autologous HSCT&#46;<a class="elsevierStyleCrossRef" href="#bib1435"><span class="elsevierStyleSup">101</span></a> In patients with poor general condition&#44; palliative chemotherapy should be administered with acceptable toxicity profile protocols&#46;</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Systemic lymphoma refractory to chemotherapy</span><p id="par0230" class="elsevierStylePara elsevierViewall">To date&#44; few treatment studies of chemoresistant NHL associated with HIV infection have been published&#46; In general&#44; the prognosis is very poor&#44; and one should choose not to treat&#44; to administer palliative chemotherapy or to consider experimental treatments&#46;</p></span></span></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Antiretroviral treatment during chemotherapy</span><p id="par0235" class="elsevierStylePara elsevierViewall">In HIV-infected patients with lymphoma&#44; cART has independently contributed to improving the response to chemotherapy and survival&#46;<a class="elsevierStyleCrossRefs" href="#bib1440"><span class="elsevierStyleSup">102&#8211;105</span></a> For this reason&#44; all HIV-infected patients with NHL should receive cART simultaneously with chemotherapy&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">A cART regimen should be selected taking into account the antiretroviral treatment history&#44; the HIV strain sensitivity&#44; the HLA-B5701 result and the hepatitis B virus &#40;HBV&#41; infection markers&#46; In some cases&#44; it is recommended to have the tropism result of the HIV strain &#40;R5&#44; X4 or dual tropism&#41;&#46; It is also important to always consider the potential pharmacological interactions and cross-toxicity between antiretrovirals and antitumor drugs or other drugs commonly used in this type of patient&#44; such as antifungals&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">There is little clinical information about the effectiveness and safety of treatment with chemotherapy and antiretrovirals&#46; In a series of 150 HIV-infected patients with cancer &#40;mostly haematological malignancies&#41; it was observed that the cART regimens based on protease inhibitors &#40;PI&#41; were less effective and less safe than those based on non-nucleoside reverse transcriptase inhibitors &#40;NNRTI&#41; and integrase strand transfer inhibitor &#40;INSTI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1460"><span class="elsevierStyleSup">106</span></a> In addition&#44; INSTI-based regimens were mostly chosen by clinicians when potentially significant interactions were anticipated between antiretrovirals&#44; chemotherapeutic agents and other drugs such as antifungals&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Between 40&#37; and 60&#37; of HIV-infected patients have been exposed to HBV&#44; and between 3&#37; and 10&#37; have chronic hepatitis B defined by the presence of HBV surface antigen &#40;HBsAg&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1465"><span class="elsevierStyleSup">107&#8211;109</span></a> Reactivation of HBV can occur during chemotherapy&#44;<a class="elsevierStyleCrossRefs" href="#bib1480"><span class="elsevierStyleSup">110&#44;111</span></a> especially when rituximab forms part of the therapeutic regimen&#46;<a class="elsevierStyleCrossRef" href="#bib1490"><span class="elsevierStyleSup">112</span></a> Patients coinfected with HIV&#47;HBV should receive a cART regimen that is also active against HBV &#40;AI&#41;&#46; Treatment should include tenofovir and emtricitabine &#40;FTC&#41; or lamivudine &#40;3TC&#41; along with a third active drug against HIV<a class="elsevierStyleCrossRef" href="#bib1495"><span class="elsevierStyleSup">113</span></a> &#40;AI&#41;&#46; Of the two existing tenofovir formulations&#44; tenofovir alafenamide &#40;TAF&#41; should preferably be used&#44; since it has a better safety profile than tenofovir disoproxil fumarate &#40;TDF&#41; and has the same activity against HBV&#46;<a class="elsevierStyleCrossRefs" href="#bib1500"><span class="elsevierStyleSup">114&#8211;116</span></a></p><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Pharmacological interactions between antiretroviral and antitumor drugs</span><p id="par0255" class="elsevierStylePara elsevierViewall">Both PIs &#40;especially ritonavir&#41;&#44; cobicistat pharmacokinetic enhancer&#44; and NNRTIs are metabolized in the liver and may be inhibitors or inducers of the CYP3A4 isoenzyme&#46; Therefore&#44; these antiretroviral drugs can alter the pharmacokinetics of antitumor drugs that are substrates of this isoenzyme&#44; especially taxanes and alkylating agents such as cyclophosphamide and etoposide&#44; and to a lesser extent&#44; vinca alkaloids&#44; antitumor antibiotics and platinum&#46; There are no relevant interactions between antiretrovirals and anthracyclines because they are metabolized by the aldo-cetorreductase enzyme&#46; Decreased clearance of cyclophosphamide and increased frequency of severe anaemia and neutropenia have been reported in patients receiving CHOP and cART compared with patients only treated with CHOP&#44;<a class="elsevierStyleCrossRef" href="#bib1515"><span class="elsevierStyleSup">117</span></a> as well as severe cases of neutropenia and mucositis in patients receiving concomitant chemotherapy based on cyclophosphamide&#44; doxorubicin and etoposide&#44; and PI-based cART&#46;<a class="elsevierStyleCrossRef" href="#bib1520"><span class="elsevierStyleSup">118</span></a> Nucleoside or nucleotide reverse transcriptase inhibitors &#40;NRTIs&#41; have little potential for pharmacokinetic interaction with cytostatics&#46; Maraviroc&#44; a CCR5 receptor antagonist&#44; is a substrate for the CYP3A enzyme and the P glycoprotein&#46; For this reason&#44; levels of maraviroc could be modified in the presence of potent CYP3A inducers or inhibitors&#46; INSTI &#40;raltegravir and dolutegravir&#41; are metabolized in the liver by glucuronidation and have little interaction with cytostatic drugs&#46; Elvitegravir&#44; a third drug in this family&#44; needs to be co-administered with the cobicistat enhancer&#44; so that for all purposes their interactions are similar to those of the PI&#46; No pharmacokinetic interactions have been described between antiretrovirals and rituximab&#44; the most widely used monoclonal antibody for the treatment of NHL&#46;<a class="elsevierStyleCrossRef" href="#bib1525"><span class="elsevierStyleSup">119</span></a> Recently&#44; a comprehensive review of antiretroviral and antitumor interactions has been published&#44;<a class="elsevierStyleCrossRef" href="#bib1530"><span class="elsevierStyleSup">120</span></a> an aspect that can also be consulted on specialized web pages&#46;</p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Cross toxicities</span><p id="par0260" class="elsevierStylePara elsevierViewall">When choosing a cART regimen&#44; it is also very important to consider the safety profile of the drugs&#46; Currently&#44; the most used NRTIs for the treatment of HIV are 3TC&#44; FTC&#44; abacavir &#40;AUC&#41; and TDF or TAF&#46; 3TC&#44; FTC&#44; TDF and TAF are also active drugs against HBV&#46; 3TC&#44; FTC and ABC lack cross-toxicity with antineoplastic drugs&#46; TDF can produce proximal tubular nephropathy and decreased glomerular filtration rate&#44;<a class="elsevierStyleCrossRef" href="#bib1535"><span class="elsevierStyleSup">121</span></a> and for this reason the use of TDF should be avoided in patients with renal insufficiency&#44; tumour lysis syndrome or in those who receive antitumor drugs with nephrotoxic potential&#46; TAF is equivalent in efficacy to TDF and lacks nephrotoxic potential&#44; at least in the short term&#46;<a class="elsevierStyleCrossRef" href="#bib1540"><span class="elsevierStyleSup">122</span></a> There are other NRTIs that are barely used today&#44; such as zidovudine &#40;AZT&#41;&#44; didanosine &#40;ddI&#41; and stavudine &#40;d4T&#41;&#44; which present significant cross-toxicity with some antitumor drugs&#46; AZT has myelotoxic potential and may enhance the haematological toxicity of different chemotherapeutic regimens&#46; ddI and d4T can produce mitochondrial toxicity and can enhance the peripheral neuropathy characteristic of some antitumor drugs such as platinum&#44; taxanes and vinca alkaloids&#46;<a class="elsevierStyleCrossRef" href="#bib1530"><span class="elsevierStyleSup">120</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">Some PIs&#44; such as atazanavir&#44; lopinavir and saquinavir&#44; may prolong the CT interval&#44; which should be taken into account if they are administered together with antineoplastic drugs such as anthracyclines&#44; which are also associated with prolongation of the CT interval&#46; In patients with hepatopathy&#44; bilirubin levels can be used to adjust the dose of some antitumor drugs&#46; In these cases&#44; treatment with atazanavir can make this adjustment difficult&#44; given that this antiretroviral is frequently associated with unconjugated hyperbilirubinemia by inhibition of the uridine diphosphate glucuronosyltransferase 1A1 &#40;UGT1A1&#41;&#46;</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Recommendations</span><p id="par0270" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0275" class="elsevierStylePara elsevierViewall">HIV-infected patients with NHL should receive cART concomitantly with chemotherapy &#40;AII&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0280" class="elsevierStylePara elsevierViewall">The cART regimens of choice in patients with NHL receiving chemotherapy treatment are those based on an INSTI such as raltegravir &#40;with which there is more experience&#41; or dolutegravir&#44; in combination with AUC&#47;3TC or FTC&#47;TAF &#40;AII&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0285" class="elsevierStylePara elsevierViewall">Treatment with other antiretroviral drugs may be indicated in some circumstances&#46; The use of PI and cobicistat should be avoided as much as possible due to the frequency of their drug interactions&#46; The use of TDF should also be avoided in patients with circumstances that increase the risk of renal toxicity &#40;BII&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0290" class="elsevierStylePara elsevierViewall">In the presence of HBV infection&#44; the therapeutic regimen should include FTC&#47;TAF as a preferred regimen or FTC&#47;TDF as an alternative &#40;AI&#41;&#46;</p></li></ul></p></span></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Complementary treatments</span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Supportive treatment for tumour lysis syndrome</span><p id="par0295" class="elsevierStylePara elsevierViewall">Patients with large tumour mass may present complications derived from the tumour lysis syndrome at the time of diagnosis or after starting chemotherapy&#46; In cases in which this complication is foreseeable&#44; due to tumour volume or very high levels of LDH and uric acid&#44; the administration of chemotherapy should be preceded by a preventive treatment with hyperhydration&#44; forced diuresis and administration of allopurinol&#46; You can also use rasburicase&#44; a recombinant form of the urate oxidase enzyme that converts uric acid into allantoin&#44; which is eliminated more easily by the kidneys&#46; This drug is more effective than allopurinol in reducing the plasma levels of uric acid and can prevent excessive delay in the start of chemotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib1545"><span class="elsevierStyleSup">123&#44;124</span></a> The recommended dose of rasburicase is 0&#46;20<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day intravenously in 50<span class="elsevierStyleHsp" style=""></span>ml of normal saline for 30<span class="elsevierStyleHsp" style=""></span>min&#46; The duration of treatment ranges from 5 to 7 days&#44; although the shorter duration regimens seem equally effective&#46;</p></span><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Colony-stimulating factors</span><p id="par0300" class="elsevierStylePara elsevierViewall">The administration of granulocyte colony stimulating factors &#40;G-CSF&#41; is recommended to shorten the duration of post-chemotherapy neutropenia&#44; to counteract the poor tolerance to cytostatics and to be able to use full doses and adequate intervals of chemotherapy &#40;AI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1555"><span class="elsevierStyleSup">125</span></a> Filgrastim at a dose of 5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg on days 7&#8211;12 is recommended with CHOP&#46; The same doses will be administered with EPOCH from day 6&#176; of the cycle to achieve an absolute number of neutrophils greater than 1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;l for two consecutive days&#46; With CODOX-M&#47;IVAC&#44; the treatment with filgrastim should be started on day 13 of the A regimen and on the day 7 of the B regimen until the next cycle or until you get a neutrophil count greater than 1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;l&#46; If other therapeutic regimens are used&#44; its use will be adapted to them&#46;</p></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Prophylaxis of opportunistic infections associated with HIV infection</span><p id="par0305" class="elsevierStylePara elsevierViewall">After the administration of chemotherapy&#44; the total number of CD4&#43; T lymphocytes decreases in 30&#8211;50&#37; with respect to the baseline&#44; depending on the intensity of the treatment and the moment in which the analysis is carried out&#46; This is the reason why in these patients the risk of opportunistic infections associated with HIV is greater than in patients without NHL in a similar stage&#46; In principle&#44; it should be said that primary or secondary prophylaxis that are the indicated according to the CD4&#43; T lymphocyte count and the previous history of opportunistic infections<a class="elsevierStyleCrossRef" href="#bib1560"><span class="elsevierStyleSup">126</span></a> should be performed&#44; although it is recommended to consider that the degree of immunosuppression of patients is greater than the one shown by the CD4&#43; T lymphocyte count at the time of tumour diagnosis and that these lymphocyte markers should be monitored throughout the treatment of the lymphoma&#44; acting accordingly&#46; <span class="elsevierStyleItalic">Pneumocystis jirovecii</span> prophylaxis is recommended for all patients &#40;AII&#41;&#46; Anti-CMV prophylaxis is generally not recommended&#44; but close monitoring with periodic blood PCR determinations for this virus in those patients with a CD4&#43; T lymphocyte count &#60;100&#47;mm is recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0945"><span class="elsevierStyleSup">3</span></a> In cases in which CMV viraemia is detected&#44; fundoscopy should be performed to rule out retinitis&#44; and regardless of the result&#44; the administration of anti-CMV treatment should be considered&#46;</p></span><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Prophylaxis and treatment of infections associated with neutropenia</span><p id="par0310" class="elsevierStylePara elsevierViewall">Neutropenia&#44; a common complication during the treatment of lymphoma&#44; is a well-known risk factor for serious bacterial and fungal infections&#46; In patients with fever and neutropenia&#44; empirical antibiotic treatment should be started without delay after taking blood and urine cultures &#40;A1&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1565"><span class="elsevierStyleSup">127&#8211;129</span></a> Antibiotic prophylaxis is a controversial issue in this group of patients&#46; Prophylaxis is considered acceptable in some guidelines with patients who have high-risk factors for infection&#44; such as those receiving intensive chemotherapy regimens or recipients of HSCT&#44; in whom deep and prolonged neutropenia is frequent &#40;&#8804;100<span class="elsevierStyleHsp" style=""></span>neutrophils&#47;mm<span class="elsevierStyleSup">3</span> during &#62;7 days&#41;&#46; However&#44; we must take into account the effects that this practice can have&#44; if carried out systematically&#44; on antibiotic resistance and other undesirable effects&#44; such as <span class="elsevierStyleItalic">Clostridium difficile colitis</span>&#46;</p></span><span id="sec0180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Vaccinations</span><p id="par0315" class="elsevierStylePara elsevierViewall">Annual inactivated influenza vaccination is indicated both in patients with HIV infection and in patients with lymphoma&#46; In the case of the latter&#44; influenza vaccination of close contacts is also recommended &#40;AI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1580"><span class="elsevierStyleSup">130</span></a> Although the optimal time to administer the influenza vaccine is unknown&#44; it is recommended to administer it at least 2 weeks before starting chemotherapy or at least one week after the last cycle &#40;B-III&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1570"><span class="elsevierStyleSup">128</span></a> These patients&#44; like all those infected with HIV&#44; should also receive vaccination against pneumococcus&#44; HBV and hepatitis A virus&#46;<a class="elsevierStyleCrossRefs" href="#bib1585"><span class="elsevierStyleSup">131&#44;132</span></a></p></span></span><span id="sec0185" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Primary lymphoma of the central nervous system associated with HIV infection</span><p id="par0320" class="elsevierStylePara elsevierViewall">PCNSL is an NHL limited to the craniospinal axis&#44; in most cases of B lineage&#46;<a class="elsevierStyleCrossRef" href="#bib1595"><span class="elsevierStyleSup">133</span></a> Its incidence increased considerably with the AIDS epidemic&#44; although it experienced a significant decrease after the introduction of cART&#46; In the early years of the epidemic&#44; the prognosis of PCNSL associated with HIV infection was very poor&#44; with median survival around 3 months or slightly more after receiving radiotherapy&#46; The prognosis has improved with cART&#44; which has allowed a better virologic control&#44; immunological improvement and decrease in the incidence of opportunistic infections&#46; These recommendations will emphasize two clinical aspects of PCNSL associated with HIV infection&#58; the diagnostic procedure and the most appropriate antitumor treatment&#46;</p><span id="sec0190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">Diagnosis</span><p id="par0325" class="elsevierStylePara elsevierViewall">In patients with HIV infection&#44; PCNSL usually occurs in highly immunosuppressed patients&#44; with CD4&#43; T lymphocyte values less than 50&#47;mm<span class="elsevierStyleSup">3</span>&#44; and it constitutes an AIDS-defining disease in approximately a third of cases&#46; There is no clinical data that is specific to this tumour&#44; so this diagnosis should be considered in HIV-infected patients with CNS involvement&#46; The context in which both PCNSL and cerebral toxoplasmosis occur&#44; and the similarity of their clinical and radiological manifestations means that the differential diagnosis between both diseases is frequently raised&#46; In these cases&#44; it is useful to have imaging tests &#40;CT or MRI&#41; and to know the CD4&#43; T lymphocyte count and the result of serology &#40;IgG&#41; for <span class="elsevierStyleItalic">Toxoplasma gondii</span>&#46;</p><span id="sec0195" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">Cranial computed tomography</span><p id="par0330" class="elsevierStylePara elsevierViewall">Cranial CT is the most used initial imaging test in patients with HIV infection and neurological manifestations&#44; but PCNSL lesions can be indistinguishable from those of toxoplasmosis&#46; In the first case&#44; there is one single lesion and usually large&#46; They are normally necrotic masses&#44; occasionally haemorrhagic&#44; poorly-defined&#44; with irregular margins&#44; with variable mass effect&#44; peritumoral oedema and ring-shaped contrast uptake&#46; The site of the lesions is not an absolutely differentiating criterion either&#46; Although lesions of PCNSL are preferably supratentorial and often infiltrate deep structures &#40;periventricular regions&#44; thalamus&#44; basal lymph nodes and corpus callosum&#41;&#44; they can also be located in the periphery of the cerebral hemispheres&#46;<a class="elsevierStyleCrossRef" href="#bib1595"><span class="elsevierStyleSup">133</span></a></p></span><span id="sec0200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0225">Cranial magnetic resonance imaging</span><p id="par0335" class="elsevierStylePara elsevierViewall">MRI is more sensitive than CT when the lesions are small and allows to define them better when they are located in the leptomeninges or the spinal canal&#46; However&#44; the specificity of both tests is not very different&#46; There are techniques that can improve the diagnostic performance of MRI&#44; such as dynamic MRI and MR spectroscopy &#40;MRS&#41;&#46; In dynamic MRI&#44; gadolinium uptake in T1 sequences is faster and more intense in PCNSL than in toxoplasmosis&#46; In MRS&#44; the spectrum of the lesion can be compared with that of healthy tissue&#44; identifying peaks of biochemical metabolites characteristic of certain diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib1600"><span class="elsevierStyleSup">134&#44;135</span></a></p></span><span id="sec0205" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0230">Single photon emission tomography and cranial positron emission tomography</span><p id="par0340" class="elsevierStylePara elsevierViewall">Nuclear medicine techniques&#44; such as single photon emission tomography &#40;SPECT&#41; with thallium-201 and PET&#44; can help in the differential diagnosis&#46; SPECT studies with thallium-201 performed in patients with PCNSL show a lesion uptake because there is an active transport of thallium-201 inside the neoplastic cells&#44; which does not happen in cerebral toxoplasmosis&#46; SPECT with thallium-201 has some limitations&#44; since it does not detect lesions smaller than 6<span class="elsevierStyleHsp" style=""></span>mm or leptomeningeal lesions or near the cranial base or the calotte&#46; In addition&#44; glucocorticoids can stabilize thallium uptake&#46; For the diagnosis of PCNSL&#44; SPECT has a sensitivity of 75&#37; and a specificity of 97&#37; and&#44; in the opinion of some authors&#44; a positive result would be an indication of performing an early stereotactic brain biopsy&#46; In other studies&#44; the diagnostic yield of the technique has been improved through the assessment of early or late uptake and the calculation of the thallium retention index&#46;<a class="elsevierStyleCrossRef" href="#bib1610"><span class="elsevierStyleSup">136</span></a> PET uses metabolites such as 18 fluorodeoxyglucose &#40;FDG&#41;&#44; which is captured by cells with high metabolic activity and high energy consumption&#44; such as malignant cells&#46; The diagnostic role of PET for the diagnosis of PCNSL is not totally clear&#46;<a class="elsevierStyleCrossRef" href="#bib1615"><span class="elsevierStyleSup">137</span></a></p></span><span id="sec0210" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0235">Analysis of cerebrospinal fluid</span><p id="par0345" class="elsevierStylePara elsevierViewall">CSF analysis can help the diagnosis of PCNSL&#44; so it should be done as long as it does not pose a risk to the patient&#46; When there is a periventricular or meningeal condition&#44; tumour cells can be identified in the CSF&#46; By means of cytofluorometry&#44; in situ hybridization or polymerase chain reaction &#40;PCR&#41;&#44; populations of monoclonal lymphocytes of a neoplastic nature and sequences of the Epstein-Barr virus &#40;EBV&#41; genome can be detected in the nucleus of said cells&#46; In some studies&#44; a good diagnostic correlation has been observed between stereotactic brain biopsy and PCR for EBV in CSF&#44; especially in patients with negative serology&#46; <span class="elsevierStyleItalic">T&#46; gondii</span> and single radiological lesion&#46;<a class="elsevierStyleCrossRefs" href="#bib1615"><span class="elsevierStyleSup">137&#8211;139</span></a> However&#44; most patients with PCNSL require a diagnosis by biopsy&#46;</p></span><span id="sec0215" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0240">Brain biopsy</span><p id="par0350" class="elsevierStylePara elsevierViewall">Stereotactic brain biopsy is the diagnostic technique of choice&#46; When carried out by experienced teams&#44; it allows to establish the diagnosis in 96&#37; of cases&#44; with few complications&#46;<a class="elsevierStyleCrossRef" href="#bib1630"><span class="elsevierStyleSup">140</span></a> In a recent meta-analysis&#44; the morbidity of this procedure in patients with PCNSL was 5&#46;1&#37;&#44; with bleeding being the most common complication&#46;<a class="elsevierStyleCrossRef" href="#bib1635"><span class="elsevierStyleSup">141</span></a></p></span></span><span id="sec0220" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0245">Practical recommendations for the diagnosis of primary central nervous system lymphoma</span><p id="par0355" class="elsevierStylePara elsevierViewall">In patients with HIV infection and space-occupying lesions &#40;SOL&#41; on CT or MRI&#44; <span class="elsevierStyleItalic">Toxoplasma</span> serology should be performed and a CD4&#43; T lymphocyte determination&#46; Different situations can occur&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">If there is a single lesion or the <span class="elsevierStyleItalic">Toxoplasma</span> serology is negative and if the situation of the patient and the type of injury allow it&#44; a lumbar puncture should be performed with study of CSF cytocentrifugate and cytofluorometry&#44; as well as a PCR for EBV and <span class="elsevierStyleItalic">Toxoplasma</span>&#46; The sum of positive tests suggestive of PCNSL &#40;including cytology and PCR for CSF EBV&#41; would strongly support the diagnosis&#44; but this should be established by brain biopsy&#46; It is important to keep in mind that anti-<span class="elsevierStyleItalic">Toxoplasma</span> empirical treatment should be administered until diagnostic confirmation is achieved&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">When the lesions are multiple&#44; and the <span class="elsevierStyleItalic">Toxoplasma</span> serology is positive&#44; empirical anti-<span class="elsevierStyleItalic">Toxoplasma</span> treatment must be administered during 2 weeks&#46; If after this period there is resolution or clinical and radiological improvement&#44; the diagnosis of cerebral toxoplasmosis can be assumed&#46; Otherwise&#44; a stereotactic brain biopsy should be performed as soon as possible&#46;</p></span><span id="sec0225" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0250">Treatment of primary central nervous system lymphoma</span><p id="par0370" class="elsevierStylePara elsevierViewall">At present&#44; it is not known which the best treatment for PCNSL in a HIV-infected patient is&#46; However&#44; considering the better prognosis of these patients with the new antiretroviral treatments&#44; the treatment regimens used in patients without HIV infection could be adopted&#46;</p><p id="par0375" class="elsevierStylePara elsevierViewall">In general&#44; the best therapeutic results in PCNSL have been achieved with high doses of methotrexate &#40;MTX-HA&#41; alone or in combination with other drugs&#46; Radiation therapy has important neurological toxicity&#44; especially in elderly patients&#44; and is currently reserved for salvage therapy or patients with very poor general condition who cannot receive chemotherapy&#46;</p><span id="sec0230" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0255">Radiotherapy</span><p id="par0380" class="elsevierStylePara elsevierViewall">Radiotherapy has been the treatment of choice for PCNSL for many years and&#44; although it can provide short-term improvements&#44; relapses are frequent&#46; In a prospective trial of the <span class="elsevierStyleItalic">Radiation Therapy Oncology Group</span> &#40;RTOG-8315&#41; the median survival after radiotherapy in patients with PCNSL was one year&#46;<a class="elsevierStyleCrossRef" href="#bib1640"><span class="elsevierStyleSup">142</span></a> In patients with PCNSL associated with HIV infection&#44; the median survival has varied between 72 and 119 days&#44;<a class="elsevierStyleCrossRefs" href="#bib1645"><span class="elsevierStyleSup">143&#8211;145</span></a> although slightly higher survivals have been documented in patients treated with cART&#46;<a class="elsevierStyleCrossRef" href="#bib1660"><span class="elsevierStyleSup">146</span></a><a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the radiotherapy treatment of PCNSL based on recent publications&#46;</p></span><span id="sec0235" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0260">Combined radiotherapy and chemotherapy treatment</span><p id="par0385" class="elsevierStylePara elsevierViewall">To date&#44; all clinical trials with combined radiotherapy and chemotherapy have been conducted in patients with PCNSL not associated with HIV infection&#46; In four clinical trials of treatment with chemotherapy based on MTX-HD and radiotherapy&#44; significant neurotoxicity was observed&#44; especially in older patients&#44; with median survival between 37 and 46 months&#46;<a class="elsevierStyleCrossRefs" href="#bib1665"><span class="elsevierStyleSup">147&#8211;150</span></a> Another clinical trial with 551 newly diagnosed patients who were randomized to treatment with chemotherapy based on MTX-HD with or without holocranial radiotherapy&#44; radiotherapy did not demonstrate a prognosis improvement in patients&#46;<a class="elsevierStyleCrossRef" href="#bib1685"><span class="elsevierStyleSup">151</span></a> The published experience with this therapeutic strategy in patients with PCNSL associated with HIV infection is limited to retrospective series with a small number of cases&#46;<a class="elsevierStyleCrossRef" href="#bib1690"><span class="elsevierStyleSup">152</span></a></p></span><span id="sec0240" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0265">Chemotherapy</span><p id="par0390" class="elsevierStylePara elsevierViewall">MTX is the most effective and most used cytostatic in the treatment of PCNSL&#46; In a study with non-HIV-infected patients&#44; monotherapy with MTX-HD &#40;3&#8211;8<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</span>&#41; has had CR in 52&#37; of cases&#44; with a median survival of 55&#46;4 months&#44; with little toxicity&#46;<a class="elsevierStyleCrossRef" href="#bib1695"><span class="elsevierStyleSup">153</span></a> In a clinical trial comparing monotherapy with MTX-HD versus combined treatment with MTX-HD and cytosine arabinoside &#40;AraC&#41; that did not include patients with HIV infection&#44; the overall response was higher in the combined treatment arm &#40;40&#37; vs 69&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#41;&#44; group in which haematological toxicity was also observed more frequently&#46;<a class="elsevierStyleCrossRef" href="#bib1700"><span class="elsevierStyleSup">154</span></a> The available data for patients with PCNSL associated with HIV infection are limited&#46; The results of a large retrospective series of patients with PCNSL treated between 1988 and 2012 suggest that the results in the era of cART with MTX-HD-based chemotherapy &#40;with or without rituximab&#41; are superior to the results of the pre-cART era&#44; in which patients were treated mostly with radiotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib1705"><span class="elsevierStyleSup">155</span></a> The median survival in a prospective series of 15 patients treated with 6 cycles of MTX-HD &#40;3<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</span>&#41; was 290 days&#46;<a class="elsevierStyleCrossRef" href="#bib1710"><span class="elsevierStyleSup">156</span></a> In a second prospective study with 12 patients who received different MTX-HD regimens &#40;between 3 and 8<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</span>&#41;&#44; the median survival exceeded 50 months&#46;</p></span><span id="sec0245" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0270">Rituximab</span><p id="par0395" class="elsevierStylePara elsevierViewall">There are retrospective studies in patients with PCNSL with or without HIV infection suggesting that the addition of rituximab could provide an additional benefit&#46;<a class="elsevierStyleCrossRefs" href="#bib1700"><span class="elsevierStyleSup">154&#44;155&#44;157</span></a> A pilot study of treatment with MTX-HD associated with rituximab is currently being conducted in patients with PCNSL associated with HIV infection&#46;</p></span><span id="sec0250" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0275">Chemotherapy associated with an autologous hematopoietic stem cell transplant</span><p id="par0400" class="elsevierStylePara elsevierViewall">There are at least three prospective studies of sequential treatment with MTX-HD based chemotherapy followed by consolidation with autologous HSCT in patients with PCNSL without HIV infection suggesting that this therapeutic modality is feasible and can provide prolonged survival with preserved neurocognitive function and good post-transplant quality of life&#46;<a class="elsevierStyleCrossRefs" href="#bib1720"><span class="elsevierStyleSup">158&#8211;161</span></a></p></span></span><span id="sec0255" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0280">Antiretroviral treatment</span><p id="par0405" class="elsevierStylePara elsevierViewall">Antiretroviral treatment regimens&#44; anti-infective prophylaxis or other complementary treatments are the same as those indicated for systemic lymphoma&#46;</p></span><span id="sec0260" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0285">Practical recommendations for the treatment of primary central nervous system lymphoma</span><p id="par0410" class="elsevierStylePara elsevierViewall">Although there are few studies of PCNSL treatment in patients with HIV infection&#44; it is recommended to use the same treatments as for patients without HIV infection &#40;AII&#41;&#46; Patients with good general condition should be treated with one of the MTX-HD-based chemotherapy regimens designed for this tumour&#44; preferably accompanied by rituximab &#40;AII&#41;&#46; The preferred chemotherapy regimen is the combination of MTX-HD and Ara-C &#40;AI&#41;&#46; Consolidation with autologous HSCT &#40;CII&#41; can be considered in some patients&#46; Radiotherapy should be considered when chemotherapy has failed or is contraindicated &#40;BII&#41;&#46; All patients should receive cART and the anti-infective prophylaxis that are indicated &#40;AI&#41;&#46;</p></span></span><span id="sec0265" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0290">Hodgkin&#39;s lymphoma</span><p id="par0415" class="elsevierStylePara elsevierViewall">The clinical presentation of HL in HIV-infected patients has changed significantly after the introduction of cART&#46; During the first years of the epidemic&#44; patients frequently presented with advanced stages or with atypical manifestations as primary extranodal forms&#46; Although the clinical presentation also seems to have undergone some changes&#44; the characteristics of HL in HIV-positive patients remain more aggressive than in the general population&#46;<a class="elsevierStyleCrossRef" href="#bib1740"><span class="elsevierStyleSup">162</span></a> The introduction of cART has also meant a radical change in the prognosis of HIV-infected patients and HL&#44; and information from different series shows that at present the prognosis of these patients can be compared to that of patients without HIV infection&#46;<a class="elsevierStyleCrossRefs" href="#bib1745"><span class="elsevierStyleSup">163&#8211;165</span></a></p><span id="sec0270" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0295">Diagnosis&#44; extension study and factors related to the prognosis</span><p id="par0420" class="elsevierStylePara elsevierViewall">The same criteria mentioned in the NHL section on the need for a histological study of a complete lymph node or a broad biopsy of infiltrated tissue are applied with HL&#46; The same applies to the complementary tests for the extension study&#44; with special emphasis on performing a baseline PET-CT study for all patients&#46; In contrast&#44; the bone marrow study would only be indicated when there is a high suspicion of infiltration&#44; such as when peripheral cytopenia is detected&#46; The Hasenclever index&#44; commonly used to estimate the prognosis of patients with advanced HL&#44;<a class="elsevierStyleCrossRef" href="#bib1760"><span class="elsevierStyleSup">166</span></a> also applies to patients with HIV infection&#46;<a class="elsevierStyleCrossRefs" href="#bib1765"><span class="elsevierStyleSup">167&#44;168</span></a> This system includes 7 factors&#44; each of which reduces the probability of disease control to 5 years by 7&#8211;8&#37; &#40;age &#8805;45 years&#44; male&#44; staging IV&#44; albumin &#60;4<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; haemoglobin &#60;10&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; leukocytes &#8805;15<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47; and lymphocytes &#60;0&#46;6<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;l &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span><span id="sec0275" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0300">Treatment</span><p id="par0425" class="elsevierStylePara elsevierViewall">In the era of cART&#44; the results of the treatment of HL in patients with HIV infection with chemotherapy regimens normally used in the treatment of this tumour &#40;ABVD&#44; Stanford V or BEACOPP&#41; do not differ substantially from those obtained in the general population &#40;AI&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1745"><span class="elsevierStyleSup">163&#44;164&#44;167&#44;169&#8211;171</span></a> For this reason&#44; in patients with HIV infection and HL&#44; the same recommendations should be followed for the first-line treatment of this tumour indicated for the general population&#46;<a class="elsevierStyleCrossRef" href="#bib1790"><span class="elsevierStyleSup">172</span></a></p><p id="par0430" class="elsevierStylePara elsevierViewall">For patients with HIV infection and HL refractory to a first-line chemotherapy or relapse&#44; salvage therapy should be identical to that of the general population not infected with HIV&#58; second-line chemotherapy with ESHAP&#44; DHAP or ICE type regimens&#44; among others&#44; and in case of chemosensitivity&#44; consolidation with autologous HSCT&#46;<a class="elsevierStyleCrossRef" href="#bib1425"><span class="elsevierStyleSup">99</span></a> Exceptionally&#44; in selected cases&#44; the implementation of an allogeneic HSCT with reduced intensity conditioning could be considered&#46;</p><p id="par0435" class="elsevierStylePara elsevierViewall">In patients with refractory or relapsed HL after autologous HSCT&#44; treatments with new forms of immunotherapy can be proposed&#44; particularly brentuximab vedotin&#46;<a class="elsevierStyleCrossRef" href="#bib1795"><span class="elsevierStyleSup">173</span></a> Currently&#44; clinical trials are underway to determine the role of brentuximab in combination with chemotherapy in HIV-infected patients with HL&#46; Although no information is available on the efficacy of PD-1&#47;PDL-1 inhibitors &#40;<span class="elsevierStyleItalic">Programmed cell death protein 1&#47;Programmed death-ligand 1</span>&#41; in HIV-infected patients with relapsed HL&#44; there is enough information to support its efficacy in patients with HL who are not infected with HIV&#46;<a class="elsevierStyleCrossRef" href="#bib1800"><span class="elsevierStyleSup">174</span></a></p><p id="par0440" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0035">Table 7</a> lists the practical recommendations for the treatment of HL in HIV-infected population&#46; It is important to bear in mind that these patients must follow the same recommendations on cART and complementary treatments applicable to patients with HIV infection and NHL&#46;</p><elsevierMultimedia ident="tbl0035"></elsevierMultimedia></span></span><span id="sec0280" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0305">Hematopoietic stem cell transplantation</span><span id="sec0285" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0310">Autologous transplant</span><p id="par0445" class="elsevierStylePara elsevierViewall">In patients with systemic NHL in first relapse and sensitive to chemotherapy&#44; without HIV infection&#44; the administration of high doses of chemotherapy&#44; with or without radiotherapy&#44; followed by an autologous HSCT&#44; is considered the treatment of choice for their rescue&#46;</p><p id="par0450" class="elsevierStylePara elsevierViewall">Different national and international groups have published their experience in autologous HSCT in patients with HIV infection&#46;<a class="elsevierStyleCrossRefs" href="#bib1425"><span class="elsevierStyleSup">99&#44;175&#8211;179</span></a> The results of all these studies allow us to conclude that autologous HSCT in HIV-infected patients with HL or NHL receiving cART is a viable&#44; safe and effective procedure&#44; with which no greater toxicity inherent to the procedure has been observed nor a substantial increase of infectious complications&#44; when compared with the group of patients with lymphoma without HIV infection&#46; Therefore&#44; autologous HSCT in this population group should be considered for the same indications as for the general population with this type of tumours &#40;<a class="elsevierStyleCrossRef" href="#tbl0040">Table 8</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0040"></elsevierMultimedia><p id="par0455" class="elsevierStylePara elsevierViewall">From the accumulated experience of the aforementioned studies&#44; the following considerations can be made about autologous HSCT in HIV-infected patients&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">1&#46;</span><p id="par0460" class="elsevierStylePara elsevierViewall">The current legal regulations regarding the specific handling and storage of hematopoietic stem cells with risk of infection transmission must be applied&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">2&#46;</span><p id="par0465" class="elsevierStylePara elsevierViewall">Mobilization of hematopoietic stem cells in these patients is similar to that obtained in patients without HIV infection&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">3&#46;</span><p id="par0470" class="elsevierStylePara elsevierViewall">The haematological and immunological recovery in these patients is comparable to that observed in patients without HIV infection and the use of G-CSF is recommended until the engraftment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">4&#46;</span><p id="par0475" class="elsevierStylePara elsevierViewall">cART must be maintained during mobilization and HSCT&#44; avoiding antiretroviral myelotoxic drugs&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">5&#46;</span><p id="par0480" class="elsevierStylePara elsevierViewall">The toxicity-related mortality rate is similar to that observed in non-HIV-infected patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">6&#46;</span><p id="par0485" class="elsevierStylePara elsevierViewall">In the conditioning of autologous HSCT in lymphoma with involvement of the CNS&#44; it is recommended to include thiotepa and BCNU &#40;HF&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1830"><span class="elsevierStyleSup">180</span></a></p></li></ul></p></span><span id="sec0290" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0315">Allogeneic hematopoietic stem cell transplantation</span><p id="par0490" class="elsevierStylePara elsevierViewall">Allogeneic HSCT has a high toxicity-related mortality &#40;20&#8211;30&#37;&#44; compared to 5&#37; in autologous HSCT&#41;&#44; which is why it has traditionally been indicated in selected patients&#44; with good general condition&#44; in whom an autologous HSCT could not be carried out due to insufficient mobilization of hematopoietic stem cells and that had a family donor with identical histocompatibility antigens&#46; In patients with HIV infection&#44; the experience with allogeneic HSCT is more limited than with autologous HSCT&#44; but it has been spreading in recent years&#44; including the use of alternative donors&#46;<a class="elsevierStyleCrossRefs" href="#bib1835"><span class="elsevierStyleSup">181&#8211;186</span></a></p><p id="par0495" class="elsevierStylePara elsevierViewall">The indications and procedures of allogeneic HSCT in these patients are similar to those used in patients without HIV infection&#46; However&#44; several aspects must be taken into special consideration in this population&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">1&#46;</span><p id="par0500" class="elsevierStylePara elsevierViewall">Toxicity-related mortality is higher than in patients without HIV infection&#44; so the procedure should be carried out in centres with experience in HSCT in high-risk patients and in close collaboration with professionals with experience in the treatment of HIV infection&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">2&#46;</span><p id="par0505" class="elsevierStylePara elsevierViewall">Supportive treatment is very important and should include adequate anti-infective prophylaxis and close follow-up after transplantation due to the high risk of mortality associated with infections&#44; especially in patients with active graft-versus-host disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">3&#46;</span><p id="par0510" class="elsevierStylePara elsevierViewall">cART must be maintained throughout the procedure&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">4&#46;</span><p id="par0515" class="elsevierStylePara elsevierViewall">cART of choice is indicated in the corresponding section of these guidelines&#46;</p></li></ul></p></span><span id="sec0295" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0320">Stem cell transplantation and HIV eradication</span><p id="par0520" class="elsevierStylePara elsevierViewall">Allogeneic hematopoietic stem cell transplantation carrying the homozygous mutation for the &#916;32 deletion of the chemokine receptor CCR5 &#40;which makes the cell resistant to HIV entry with tropism R5&#41; has allowed the eradication of HIV from a patient with high-risk leukaemia in which there is no evidence of virus presence after 8 years of sustained ART discontinuation&#46;<a class="elsevierStyleCrossRef" href="#bib1840"><span class="elsevierStyleSup">182</span></a> This case&#44; known as the &#8220;Berlin patient&#8221;&#44; illustrates that it is possible to cure HIV infection&#46; In addition&#44; the study of the possible mechanisms involved in the eradication of HIV in this patient has served to advance in different aspects related to the cure of this viral infection&#46;<a class="elsevierStyleCrossRef" href="#bib1855"><span class="elsevierStyleSup">185</span></a> Therefore&#44; although the choice of the donor in patients with HIV infection in whom allogeneic transplantation is indicated should be carried out following the same criteria as in patients without HIV infection&#44; it is recommended to explore the availability of a source of stem cells with a homozygous mutation for the &#916;32 deletion of the chemokine receptor CCR5 as a possible strategy for the cure of HIV infection&#46;</p></span></span><span id="sec0300" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0325">Funding</span><p id="par0525" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleGrantSponsor" id="gs1">Spanish AIDS Research Network</span> &#40;RIS&#41;&#46; Cooperative Health Research Networks &#40;RETICS&#41;&#44; projects RD16&#47;0025&#47;0017 and RD12&#47;0036&#47;0029&#44; as part of the National Plan R&#43;D&#43;I co-financed by <span class="elsevierStyleGrantSponsor" id="gs2">ISCIII-General Evaluation Subdirectorate</span> and the <span class="elsevierStyleGrantSponsor" id="gs3">European Regional Development Fund</span> &#40;ERDF&#41;&#46;</p></span><span id="sec0305" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0330">Conflict of interest</span><p id="par0530" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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              "identificador" => "sec0030"
              "titulo" => "Treatment"
              "secciones" => array:7 [
                0 => array:2 [
                  "identificador" => "sec0035"
                  "titulo" => "Diffuse large B-cell lymphoma"
                ]
                1 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Aggressive B-cell lymphoma with MYC and BCL2 and&#47;or BCL6 gene rearrangement"
                ]
                2 => array:2 [
                  "identificador" => "sec0045"
                  "titulo" => "Burkitt&#39;s lymphoma"
                ]
                3 => array:2 [
                  "identificador" => "sec0050"
                  "titulo" => "Plasmablastic lymphoma"
                ]
                4 => array:2 [
                  "identificador" => "sec0055"
                  "titulo" => "Primary effusion lymphoma"
                ]
                5 => array:2 [
                  "identificador" => "sec0060"
                  "titulo" => "Multicentric Castleman&#39;s disease"
                ]
                6 => array:3 [
                  "identificador" => "sec0065"
                  "titulo" => "Lymphomatous meningitis"
                  "secciones" => array:3 [
                    0 => array:2 [ …2]
                    1 => array:2 [ …2]
                    2 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "sec0085"
              "titulo" => "Practical recommendations for the treatment of systemic lymphomas in HIV-infected patients"
              "secciones" => array:6 [
                0 => array:2 [
                  "identificador" => "sec0090"
                  "titulo" => "Diffuse large B-cell lymphoma"
                ]
                1 => array:2 [
                  "identificador" => "sec0095"
                  "titulo" => "Burkitt&#39;s lymphoma"
                ]
                2 => array:2 [
                  "identificador" => "sec0100"
                  "titulo" => "Aggressive B-cell lymphoma with MYC and BCL2 and&#47;or BCL6 gene rearrangement"
                ]
                3 => array:2 [
                  "identificador" => "sec0105"
                  "titulo" => "Plasmablastic lymphoma"
                ]
                4 => array:2 [
                  "identificador" => "sec0110"
                  "titulo" => "Multicentric Castleman&#39;s disease"
                ]
                5 => array:2 [
                  "identificador" => "sec0115"
                  "titulo" => "Primary effusion lymphoma"
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "sec0120"
              "titulo" => "Second-line treatments"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0125"
                  "titulo" => "Relapsed systemic lymphoma"
                ]
                1 => array:2 [
                  "identificador" => "sec0130"
                  "titulo" => "Systemic lymphoma refractory to chemotherapy"
                ]
              ]
            ]
          ]
        ]
        7 => array:3 [
          "identificador" => "sec0135"
          "titulo" => "Antiretroviral treatment during chemotherapy"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0140"
              "titulo" => "Pharmacological interactions between antiretroviral and antitumor drugs"
            ]
            1 => array:2 [
              "identificador" => "sec0145"
              "titulo" => "Cross toxicities"
            ]
            2 => array:2 [
              "identificador" => "sec0150"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        8 => array:3 [
          "identificador" => "sec0155"
          "titulo" => "Complementary treatments"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0160"
              "titulo" => "Supportive treatment for tumour lysis syndrome"
            ]
            1 => array:2 [
              "identificador" => "sec0165"
              "titulo" => "Colony-stimulating factors"
            ]
            2 => array:2 [
              "identificador" => "sec0170"
              "titulo" => "Prophylaxis of opportunistic infections associated with HIV infection"
            ]
            3 => array:2 [
              "identificador" => "sec0175"
              "titulo" => "Prophylaxis and treatment of infections associated with neutropenia"
            ]
            4 => array:2 [
              "identificador" => "sec0180"
              "titulo" => "Vaccinations"
            ]
          ]
        ]
        9 => array:3 [
          "identificador" => "sec0185"
          "titulo" => "Primary lymphoma of the central nervous system associated with HIV infection"
          "secciones" => array:5 [
            0 => array:3 [
              "identificador" => "sec0190"
              "titulo" => "Diagnosis"
              "secciones" => array:5 [
                0 => array:2 [
                  "identificador" => "sec0195"
                  "titulo" => "Cranial computed tomography"
                ]
                1 => array:2 [
                  "identificador" => "sec0200"
                  "titulo" => "Cranial magnetic resonance imaging"
                ]
                2 => array:2 [
                  "identificador" => "sec0205"
                  "titulo" => "Single photon emission tomography and cranial positron emission tomography"
                ]
                3 => array:2 [
                  "identificador" => "sec0210"
                  "titulo" => "Analysis of cerebrospinal fluid"
                ]
                4 => array:2 [
                  "identificador" => "sec0215"
                  "titulo" => "Brain biopsy"
                ]
              ]
            ]
            1 => array:2 [
              "identificador" => "sec0220"
              "titulo" => "Practical recommendations for the diagnosis of primary central nervous system lymphoma"
            ]
            2 => array:3 [
              "identificador" => "sec0225"
              "titulo" => "Treatment of primary central nervous system lymphoma"
              "secciones" => array:5 [
                0 => array:2 [
                  "identificador" => "sec0230"
                  "titulo" => "Radiotherapy"
                ]
                1 => array:2 [
                  "identificador" => "sec0235"
                  "titulo" => "Combined radiotherapy and chemotherapy treatment"
                ]
                2 => array:2 [
                  "identificador" => "sec0240"
                  "titulo" => "Chemotherapy"
                ]
                3 => array:2 [
                  "identificador" => "sec0245"
                  "titulo" => "Rituximab"
                ]
                4 => array:2 [
                  "identificador" => "sec0250"
                  "titulo" => "Chemotherapy associated with an autologous hematopoietic stem cell transplant"
                ]
              ]
            ]
            3 => array:2 [
              "identificador" => "sec0255"
              "titulo" => "Antiretroviral treatment"
            ]
            4 => array:2 [
              "identificador" => "sec0260"
              "titulo" => "Practical recommendations for the treatment of primary central nervous system lymphoma"
            ]
          ]
        ]
        10 => array:3 [
          "identificador" => "sec0265"
          "titulo" => "Hodgkin&#39;s lymphoma"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0270"
              "titulo" => "Diagnosis&#44; extension study and factors related to the prognosis"
            ]
            1 => array:2 [
              "identificador" => "sec0275"
              "titulo" => "Treatment"
            ]
          ]
        ]
        11 => array:3 [
          "identificador" => "sec0280"
          "titulo" => "Hematopoietic stem cell transplantation"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0285"
              "titulo" => "Autologous transplant"
            ]
            1 => array:2 [
              "identificador" => "sec0290"
              "titulo" => "Allogeneic hematopoietic stem cell transplantation"
            ]
            2 => array:2 [
              "identificador" => "sec0295"
              "titulo" => "Stem cell transplantation and HIV eradication"
            ]
          ]
        ]
        12 => array:2 [
          "identificador" => "sec0300"
          "titulo" => "Funding"
        ]
        13 => array:2 [
          "identificador" => "sec0305"
          "titulo" => "Conflict of interest"
        ]
        14 => array:2 [
          "identificador" => "xack359056"
          "titulo" => "Acknowledgements"
        ]
        15 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2017-08-16"
    "fechaAceptado" => "2017-11-02"
    "PalabrasClave" => array:2 [
      "en" => array:2 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1009613"
          "palabras" => array:5 [
            0 => "Non-Hodgkin&#39;s lymphoma"
            1 => "Hodgkin&#39;s lymphoma"
            2 => "HIV"
            3 => "AIDS"
            4 => "Antiretroviral therapy"
          ]
        ]
        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec1009612"
          "palabras" => array:76 [
            0 => "ABC"
            1 => "ABVD"
            2 => "Ara-C"
            3 => "AZT"
            4 => "BCNU"
            5 => "BEACOPP"
            6 => "CDC"
            7 => "CHOP"
            8 => "CMV"
            9 => "CODOX-M&#47;IVAC"
            10 => "d4"
            11 => "dd"
            12 => "DH"
            13 => "DHAP"
            14 => "MCD"
            15 => "EPOCH"
            16 => "AD-EPOCH-R EPOCH-R"
            17 => "MRS"
            18 => "ESHAP"
            19 => "FDG18"
            20 => "FTC"
            21 => "G-CSF"
            22 => "GESID"
            23 => "Gy"
            24 => "HBs"
            25 => "HHV-8"
            26 => "Hyper-CVAD"
            27 => "ICE"
            28 => "IL-6"
            29 => "IMRT"
            30 => "INSTI"
            31 => "PI"
            32 => "IPI"
            33 => "IT"
            34 => "NRTI"
            35 => "NNRTI"
            36 => "LANA-1"
            37 => "BL"
            38 => "DLBCL"
            39 => "CSF"
            40 => "LDH"
            41 => "HL"
            42 => "LMP1"
            43 => "NHL"
            44 => "SOL"
            45 => "PCNSL"
            46 => "Lymphomatous LM"
            47 => "MTX"
            48 => "MTX-HD"
            49 => "PCR"
            50 => "PD-1&#47;PDL-1"
            51 => "PET-CT"
            52 => "PETHEM"
            53 => "CT"
            54 => "R-CHOEPR-CHOP"
            55 => "R-CHOP"
            56 => "R-EPOCH"
            57 => "CR"
            58 => "RT"
            59 => "MRI"
            60 => "OS"
            61 => "KS"
            62 => "EFS"
            63 => "SNC"
            64 => "SPECT"
            65 => "Stanford V"
            66 => "TAF"
            67 => "cART"
            68 => "TDF"
            69 => "TH"
            70 => "HSCT"
            71 => "3TC"
            72 => "UGT1A1"
            73 => "EBV"
            74 => "HBV"
            75 => "HIV"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1009614"
          "palabras" => array:5 [
            0 => "Linfoma no hodgkiniano"
            1 => "Linfoma de Hodgkin"
            2 => "VIH"
            3 => "Sida"
            4 => "Tratamiento antirretroviral"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The incidence of non-Hodgkin&#39;s lymphoma and Hodgkin&#39;s lymphoma is higher in patients with HIV infection than in the general population&#46; Following the introduction of combination antiretroviral therapy &#40;cART&#41;&#44; the prognostic significance of HIV-related variables has decreased&#44; and lymphoma-related factors have become more pronounced&#46; Currently&#44; treatments for lymphomas in HIV-infected patients do not differ from those used in the general population&#46; However&#44; differentiating characteristics of seropositive patients&#44; such as the need for cART and specific prophylaxis and treatment of certain opportunistic infections&#44; should be considered&#46; This document updates recommendations on the diagnosis and treatment of lymphomas in HIV infected patients published by GESIDA&#47;PETHEMA in 2008&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La incidencia de linfoma no hodgkiniano y linfoma de Hodgkin es mayor en pacientes con infecci&#243;n por el VIH que en la poblaci&#243;n general&#46; Tras la introducci&#243;n del tratamiento antirretroviral de combinaci&#243;n &#40;TARc&#41; ha disminuido la importancia pron&#243;stica de variables relacionadas con el VIH&#44; adquiriendo mayor peso factores relacionados con el linfoma&#46; Actualmente&#44; los tratamientos de los linfomas en pacientes infectados por VIH no difieren de los empleados en la poblaci&#243;n general&#46; Pero existen algunos aspectos diferenciales de los pacientes con VIH como la necesidad de TARc&#44; de profilaxis y de tratamientos de algunas infecciones oportunistas&#46; En este documento se actualizan las recomendaciones sobre el diagn&#243;stico y el tratamiento de los linfomas en pacientes infectados por VIH publicadas por GESIDA&#47;PETHEMA en 2008&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Miralles P&#44; Navarro JT&#44; Berenguer J&#44; G&#243;mez Codina J&#44; Kwon M&#44; Serrano D&#44; et al&#46; Recomendaciones de GESIDA&#47;PETHEMA sobre el diagn&#243;stico y tratamiento de los linfomas en pacientes infectados por el virus de la inmunodeficiencia humana&#46; Med Clin &#40;Barc&#41;&#46; 2018&#59;151&#58;39&#46;e1&#8211;39&#46;e17&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">This document is endorsed by the GESIDA groups &#40;attached to the Spanish Society of Infectious Diseases and Clinical Microbiology&#41; and PETHEMA &#40;attached to the Spanish Society of Haematology and Hemotherapy&#41;&#46;</p>"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:3 [
          0 => array:4 [
            "apendice" => "<p id="par0540" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0545" class="elsevierStylePara elsevierViewall">B-cell neoplasms<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">I&#46;</span><p id="par0550" class="elsevierStylePara elsevierViewall">Precursor B-cell neoplasms<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">-</span><p id="par0555" class="elsevierStylePara elsevierViewall">Leukaemia&#47;lymphoblastic lymphoma B</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">II&#46;</span><p id="par0560" class="elsevierStylePara elsevierViewall">Mature B-cell neoplasms<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">-</span><p id="par0565" class="elsevierStylePara elsevierViewall">B-cell chronic lymphocytic leukaemia&#47;small cell lymphocytic lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">-</span><p id="par0570" class="elsevierStylePara elsevierViewall">B-cell prolymphocytic leukaemia</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">-</span><p id="par0575" class="elsevierStylePara elsevierViewall">Splenic marginal zone lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">-</span><p id="par0580" class="elsevierStylePara elsevierViewall">Tricholeukemia</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">-</span><p id="par0585" class="elsevierStylePara elsevierViewall">Leukaemia&#47;splenic B-cell lymphoma&#44; unclassifiable</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">-</span><p id="par0590" class="elsevierStylePara elsevierViewall">Splenic diffuse red pulp small b-cell lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">-</span><p id="par0595" class="elsevierStylePara elsevierViewall">Variant of circulating villous lymphocytes</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">-</span><p id="par0600" class="elsevierStylePara elsevierViewall">Lymphoplasmacytic lymphoma and Waldenstr&#246;m macroglobulinemia</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">-</span><p id="par0605" class="elsevierStylePara elsevierViewall">Heavy-chain diseases</p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">-</span><p id="par0610" class="elsevierStylePara elsevierViewall">Alpha heavy chain disease</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">-</span><p id="par0615" class="elsevierStylePara elsevierViewall">Gamma heavy chain disease</p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">-</span><p id="par0620" class="elsevierStylePara elsevierViewall">Mu heavy chain disease</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">-</span><p id="par0625" class="elsevierStylePara elsevierViewall">Plasma cell neoplasms</p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">-</span><p id="par0630" class="elsevierStylePara elsevierViewall">Monoclonal gammopathy of uncertain significance</p></li><li class="elsevierStyleListItem" id="lsti0165"><span class="elsevierStyleLabel">-</span><p id="par0635" class="elsevierStylePara elsevierViewall">Plasma cell myeloma</p></li><li class="elsevierStyleListItem" id="lsti0170"><span class="elsevierStyleLabel">-</span><p id="par0640" class="elsevierStylePara elsevierViewall">Solitary bone plasmacytoma</p></li><li class="elsevierStyleListItem" id="lsti0175"><span class="elsevierStyleLabel">-</span><p id="par0645" class="elsevierStylePara elsevierViewall">Extraosseous plasmacytoma</p></li><li class="elsevierStyleListItem" id="lsti0180"><span class="elsevierStyleLabel">-</span><p id="par0650" class="elsevierStylePara elsevierViewall">Extranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue &#40;MALT lymphoma&#41;</p></li><li class="elsevierStyleListItem" id="lsti0185"><span class="elsevierStyleLabel">-</span><p id="par0655" class="elsevierStylePara elsevierViewall">Nodal marginal zone lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0190"><span class="elsevierStyleLabel">-</span><p id="par0660" class="elsevierStylePara elsevierViewall">Follicular lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0195"><span class="elsevierStyleLabel">-</span><p id="par0665" class="elsevierStylePara elsevierViewall">Primary cutaneous follicle centre lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0200"><span class="elsevierStyleLabel">-</span><p id="par0670" class="elsevierStylePara elsevierViewall">Mantle cell lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0205"><span class="elsevierStyleLabel">-</span><p id="par0675" class="elsevierStylePara elsevierViewall">Diffuse large B-cell lymphoma &#40;DLBCL&#41;<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0210"><span class="elsevierStyleLabel">-</span><p id="par0680" class="elsevierStylePara elsevierViewall">DLBCL &#40;without other specification&#41;</p></li><li class="elsevierStyleListItem" id="lsti0215"><span class="elsevierStyleLabel">-</span><p id="par0685" class="elsevierStylePara elsevierViewall">Morphological variants&#58;</p></li><li class="elsevierStyleListItem" id="lsti0220"><span class="elsevierStyleLabel">-</span><p id="par0690" class="elsevierStylePara elsevierViewall">Centroblastic</p></li><li class="elsevierStyleListItem" id="lsti0225"><span class="elsevierStyleLabel">-</span><p id="par0695" class="elsevierStylePara elsevierViewall">Immunoblastic</p></li><li class="elsevierStyleListItem" id="lsti0230"><span class="elsevierStyleLabel">-</span><p id="par0700" class="elsevierStylePara elsevierViewall">Anaplastic</p></li><li class="elsevierStyleListItem" id="lsti0235"><span class="elsevierStyleLabel">-</span><p id="par0705" class="elsevierStylePara elsevierViewall">Other</p></li><li class="elsevierStyleListItem" id="lsti0240"><span class="elsevierStyleLabel">-</span><p id="par0710" class="elsevierStylePara elsevierViewall">Molecular variants&#58;</p></li><li class="elsevierStyleListItem" id="lsti0245"><span class="elsevierStyleLabel">-</span><p id="par0715" class="elsevierStylePara elsevierViewall">Germinal centre</p></li><li class="elsevierStyleListItem" id="lsti0250"><span class="elsevierStyleLabel">-</span><p id="par0720" class="elsevierStylePara elsevierViewall">Activated B-cells</p></li><li class="elsevierStyleListItem" id="lsti0255"><span class="elsevierStyleLabel">-</span><p id="par0725" class="elsevierStylePara elsevierViewall">Specific subtypes&#58;</p></li><li class="elsevierStyleListItem" id="lsti0260"><span class="elsevierStyleLabel">-</span><p id="par0730" class="elsevierStylePara elsevierViewall">T-cell&#47;histiocyte rich</p></li><li class="elsevierStyleListItem" id="lsti0265"><span class="elsevierStyleLabel">-</span><p id="par0735" class="elsevierStylePara elsevierViewall">Primary central nervous system DLBCL</p></li><li class="elsevierStyleListItem" id="lsti0270"><span class="elsevierStyleLabel">-</span><p id="par0740" class="elsevierStylePara elsevierViewall">Cutaneous DLBCL&#44; leg type</p></li><li class="elsevierStyleListItem" id="lsti0275"><span class="elsevierStyleLabel">-</span><p id="par0745" class="elsevierStylePara elsevierViewall">EBV-positive DLBCL of the elderly</p></li><li class="elsevierStyleListItem" id="lsti0280"><span class="elsevierStyleLabel">-</span><p id="par0750" class="elsevierStylePara elsevierViewall">Other large B-cell lymphomas&#58;</p></li><li class="elsevierStyleListItem" id="lsti0285"><span class="elsevierStyleLabel">-</span><p id="par0755" class="elsevierStylePara elsevierViewall">Primary mediastinal DLBCL &#40;thymic&#41;</p></li><li class="elsevierStyleListItem" id="lsti0290"><span class="elsevierStyleLabel">-</span><p id="par0760" class="elsevierStylePara elsevierViewall">Intravascular lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0295"><span class="elsevierStyleLabel">-</span><p id="par0765" class="elsevierStylePara elsevierViewall">DLBCL associated with chronic inflammation</p></li><li class="elsevierStyleListItem" id="lsti0300"><span class="elsevierStyleLabel">-</span><p id="par0770" class="elsevierStylePara elsevierViewall">Lymphomatoid granulomatosis</p></li><li class="elsevierStyleListItem" id="lsti0305"><span class="elsevierStyleLabel">-</span><p id="par0775" class="elsevierStylePara elsevierViewall">ALK-positive DLBCL</p></li><li class="elsevierStyleListItem" id="lsti0310"><span class="elsevierStyleLabel">-</span><p id="par0780" class="elsevierStylePara elsevierViewall">Plasmablastic lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0315"><span class="elsevierStyleLabel">-</span><p id="par0785" class="elsevierStylePara elsevierViewall">DLBCL arising in HHV8-associated multicentric Castleman disease</p></li><li class="elsevierStyleListItem" id="lsti0320"><span class="elsevierStyleLabel">-</span><p id="par0790" class="elsevierStylePara elsevierViewall">Effusion lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0325"><span class="elsevierStyleLabel">-</span><p id="par0795" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Borderline</span> cases&#58;</p></li><li class="elsevierStyleListItem" id="lsti0330"><span class="elsevierStyleLabel">-</span><p id="par0800" class="elsevierStylePara elsevierViewall">Unclassifiable B-cell lymphoma&#44; with intermediate features between DLBCL and Burkitt&#39;s lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0335"><span class="elsevierStyleLabel">-</span><p id="par0805" class="elsevierStylePara elsevierViewall">Unclassifiable B-cell lymphoma&#44; with intermediate features between DLBCL and classic Hodgkin&#39;s lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0340"><span class="elsevierStyleLabel">-</span><p id="par0810" class="elsevierStylePara elsevierViewall">Burkitt&#39;s lymphoma</p></li></ul></p></li></ul></p></li></ul></p></li></ul><ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0345"><span class="elsevierStyleLabel">&#8226;</span><p id="par0815" class="elsevierStylePara elsevierViewall">T-cell and NK-cell neoplasms<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0350"><span class="elsevierStyleLabel">I&#46;</span><p id="par0820" class="elsevierStylePara elsevierViewall">Precursor T-cell neoplasms<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0355"><span class="elsevierStyleLabel">-</span><p id="par0825" class="elsevierStylePara elsevierViewall">Leukaemia&#47;T-cell lymphoblastic lymphoma</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0360"><span class="elsevierStyleLabel">II&#46;</span><p id="par0830" class="elsevierStylePara elsevierViewall">Peripheral T-cell and NK-cell neoplasms<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0365"><span class="elsevierStyleLabel">-</span><p id="par0835" class="elsevierStylePara elsevierViewall">T-cell prolymphocytic leukaemia</p></li><li class="elsevierStyleListItem" id="lsti0370"><span class="elsevierStyleLabel">-</span><p id="par0840" class="elsevierStylePara elsevierViewall">T-cell large granular lymphocytic leukaemia</p></li><li class="elsevierStyleListItem" id="lsti0375"><span class="elsevierStyleLabel">-</span><p id="par0845" class="elsevierStylePara elsevierViewall">Chronic lymphoproliferative disorder of NK cells</p></li><li class="elsevierStyleListItem" id="lsti0380"><span class="elsevierStyleLabel">-</span><p id="par0850" class="elsevierStylePara elsevierViewall">Aggressive NK-cell leukaemia</p></li><li class="elsevierStyleListItem" id="lsti0385"><span class="elsevierStyleLabel">-</span><p id="par0855" class="elsevierStylePara elsevierViewall">Systemic EBV&#43;T cell lymphoproliferative disease of childhood</p></li><li class="elsevierStyleListItem" id="lsti0390"><span class="elsevierStyleLabel">-</span><p id="par0860" class="elsevierStylePara elsevierViewall">Leukaemia&#47;adult T-cell lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0395"><span class="elsevierStyleLabel">-</span><p id="par0865" class="elsevierStylePara elsevierViewall">Extranodal NK&#47;T-cell lymphoma&#44; nasal type</p></li><li class="elsevierStyleListItem" id="lsti0400"><span class="elsevierStyleLabel">-</span><p id="par0870" class="elsevierStylePara elsevierViewall">T-cell lymphoma associated with enteropathy</p></li><li class="elsevierStyleListItem" id="lsti0405"><span class="elsevierStyleLabel">-</span><p id="par0875" class="elsevierStylePara elsevierViewall">Hepatosplenic T-cell lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0410"><span class="elsevierStyleLabel">-</span><p id="par0880" class="elsevierStylePara elsevierViewall">Pancreatic subcutaneous T-cell lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0415"><span class="elsevierStyleLabel">-</span><p id="par0885" class="elsevierStylePara elsevierViewall">Mycosis fungoides</p></li><li class="elsevierStyleListItem" id="lsti0420"><span class="elsevierStyleLabel">-</span><p id="par0890" class="elsevierStylePara elsevierViewall">S&#233;zary syndrome</p></li><li class="elsevierStyleListItem" id="lsti0425"><span class="elsevierStyleLabel">-</span><p id="par0895" class="elsevierStylePara elsevierViewall">T-cell lymphoproliferative disorders&#44; cutaneous&#44; CD30&#43;</p></li><li class="elsevierStyleListItem" id="lsti0430"><span class="elsevierStyleLabel">-</span><p id="par0900" class="elsevierStylePara elsevierViewall">Primary cutaneous anaplastic large-cell lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0435"><span class="elsevierStyleLabel">-</span><p id="par0905" class="elsevierStylePara elsevierViewall">Lymphomatoid papulosis</p></li><li class="elsevierStyleListItem" id="lsti0440"><span class="elsevierStyleLabel">-</span><p id="par0910" class="elsevierStylePara elsevierViewall">Primary cutaneous peripheral T-cell lymphomas &#40;rare forms&#41;</p></li><li class="elsevierStyleListItem" id="lsti0445"><span class="elsevierStyleLabel">-</span><p id="par0915" class="elsevierStylePara elsevierViewall">Primary cutaneous gamma&#47;delta T-cell lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0450"><span class="elsevierStyleLabel">-</span><p id="par0920" class="elsevierStylePara elsevierViewall">Primary cutaneous CD8&#43; aggressive epidermotropic cytotoxic T-cell lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0455"><span class="elsevierStyleLabel">-</span><p id="par0925" class="elsevierStylePara elsevierViewall">Primary cutaneous CD4-positive small&#47;medium-sized pleomorphic T-cell lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0460"><span class="elsevierStyleLabel">-</span><p id="par0930" class="elsevierStylePara elsevierViewall">Peripheral T-cell lymphoma &#40;without other specification&#41;</p></li><li class="elsevierStyleListItem" id="lsti0465"><span class="elsevierStyleLabel">-</span><p id="par0935" class="elsevierStylePara elsevierViewall">T-cell angioimmunoblastic lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0470"><span class="elsevierStyleLabel">-</span><p id="par0940" class="elsevierStylePara elsevierViewall">Anaplastic large cell lymphoma&#44; ALK&#43;</p></li><li class="elsevierStyleListItem" id="lsti0475"><span class="elsevierStyleLabel">-</span><p id="par0945" class="elsevierStylePara elsevierViewall">Anaplastic large cell lymphoma&#44; ALK&#8722;</p></li></ul></p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0480"><span class="elsevierStyleLabel">&#8226;</span><p id="par0950" class="elsevierStylePara elsevierViewall">Hodgkin&#39;s lymphoma<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0485"><span class="elsevierStyleLabel">-</span><p id="par0955" class="elsevierStylePara elsevierViewall">Nodular lymphocyte predominant Hodgkin&#39;s lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0490"><span class="elsevierStyleLabel">-</span><p id="par0960" class="elsevierStylePara elsevierViewall">Classic Hodgkin&#39;s lymphoma</p></li><li class="elsevierStyleListItem" id="lsti0495"><span class="elsevierStyleLabel">-</span><p id="par0965" class="elsevierStylePara elsevierViewall">Nodular sclerosis</p></li><li class="elsevierStyleListItem" id="lsti0500"><span class="elsevierStyleLabel">-</span><p id="par0970" class="elsevierStylePara elsevierViewall">Mixed cellularity</p></li><li class="elsevierStyleListItem" id="lsti0505"><span class="elsevierStyleLabel">-</span><p id="par0975" class="elsevierStylePara elsevierViewall">Lymphocyte-rich</p></li><li class="elsevierStyleListItem" id="lsti0510"><span class="elsevierStyleLabel">-</span><p id="par0980" class="elsevierStylePara elsevierViewall">Lymphocyte depletion</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0515"><span class="elsevierStyleLabel">&#8226;</span><p id="par0985" class="elsevierStylePara elsevierViewall">Post-transplant lymphoproliferative disorders &#40;PTLD&#41;<ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0520"><span class="elsevierStyleLabel">-</span><p id="par0990" class="elsevierStylePara elsevierViewall">Early lesions</p></li><li class="elsevierStyleListItem" id="lsti0525"><span class="elsevierStyleLabel">-</span><p id="par0995" class="elsevierStylePara elsevierViewall">Plasmacytic hyperplasia</p></li><li class="elsevierStyleListItem" id="lsti0530"><span class="elsevierStyleLabel">-</span><p id="par1000" class="elsevierStylePara elsevierViewall">Infectious mononucleosis-like PTLD</p></li><li class="elsevierStyleListItem" id="lsti0535"><span class="elsevierStyleLabel">-</span><p id="par1005" class="elsevierStylePara elsevierViewall">Polymorphic PTLD</p></li><li class="elsevierStyleListItem" id="lsti0540"><span class="elsevierStyleLabel">-</span><p id="par1010" class="elsevierStylePara elsevierViewall">Monomorphic PTLD &#40;type B or T&#47;NK cells&#41;</p></li><li class="elsevierStyleListItem" id="lsti0545"><span class="elsevierStyleLabel">-</span><p id="par1015" class="elsevierStylePara elsevierViewall">Classic Hodgkin lymphoma-type PTLD</p></li></ul></p></li></ul></p>"
            "etiqueta" => "Appendix 1"
            "titulo" => "WHO Classification of Lymphoid Neoplasms"
            "identificador" => "sec0310"
          ]
          1 => array:4 [
            "apendice" => "<p id="par1020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Stage I&#46;</span> Involvement of a single lymph node region&#44; or of a single lymphoid structure &#40;thymus&#44; spleen&#44; Waldeyer&#39;s ring&#41; or of an extralymphatic area &#40;Stage I&#8211;E&#41;&#46;</p> <p id="par1025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Stage II&#46;</span> Involvement of two or more nodal regions or of nodal and extranodal regions contiguous to the first &#40;E&#41;&#44; but always on the same side of the diaphragm&#46;</p> <p id="par1030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Stage III&#46;</span> Involvement of lymphatic regions or structures on both sides of the diaphragm&#46; There may be contiguous extranodal involvement &#40;E&#41;&#46;</p> <p id="par1035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Stage IV</span>&#46; Disseminated involvement of one or more extralymphatic organs&#46; There may or may not be lymph node involvement&#46;</p> <p id="par1040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Voluminous mass criterion</span>&#46; Nodal mass greater than 10<span class="elsevierStyleHsp" style=""></span>cm or mediastinal mass equal to or greater than 1&#47;3 of the thoracic diameter &#40;at the level of D5&#8211;D6&#41;&#46;</p> <p id="par1045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">B symptoms</span>&#46; Fever&#44; night sweats or weight loss &#40;more than 10&#37; in six months&#41;&#46;</p>"
            "etiqueta" => "Appendix 2"
            "titulo" => "Staging of lymphomas according to Ann Arbor&#47;Cotswolds"
            "identificador" => "sec0315"
          ]
          2 => array:4 [
            "apendice" => "<p id="par1050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Limited stages</span></p> <p id="par1055" class="elsevierStylePara elsevierViewall">Stage I<ul class="elsevierStyleList" id="lis0075"><li class="elsevierStyleListItem" id="lsti0550"><span class="elsevierStyleLabel">-</span><p id="par1060" class="elsevierStylePara elsevierViewall">Involvement of a lymph node or several adjacent lymph nodes or</p></li><li class="elsevierStyleListItem" id="lsti0555"><span class="elsevierStyleLabel">-</span><p id="par1065" class="elsevierStylePara elsevierViewall">Single extranodal involvement without lymph node involvement</p></li></ul></p> <p id="par1070" class="elsevierStylePara elsevierViewall">Stage II<ul class="elsevierStyleList" id="lis0080"><li class="elsevierStyleListItem" id="lsti0560"><span class="elsevierStyleLabel">-</span><p id="par1075" class="elsevierStylePara elsevierViewall">Involvement of one or more nodal groups on one side of the diaphragm or</p></li><li class="elsevierStyleListItem" id="lsti0565"><span class="elsevierStyleLabel">-</span><p id="par1080" class="elsevierStylePara elsevierViewall">Stage I or II by lymph node involvement&#44; with extranodal extension by contiguity</p></li><li class="elsevierStyleListItem" id="lsti0570"><span class="elsevierStyleLabel">-</span><p id="par1085" class="elsevierStylePara elsevierViewall">Stage II with bulky mass</p></li><li class="elsevierStyleListItem" id="lsti0575"><span class="elsevierStyleLabel">-</span><p id="par1090" class="elsevierStylePara elsevierViewall">Stage I or II with criterion of voluminous mass</p></li></ul></p> <p id="par1095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Advanced stages</span></p> <p id="par1100" class="elsevierStylePara elsevierViewall">Stage III<ul class="elsevierStyleList" id="lis0085"><li class="elsevierStyleListItem" id="lsti0580"><span class="elsevierStyleLabel">-</span><p id="par1105" class="elsevierStylePara elsevierViewall">Lymph node involvement on both sides of the diaphragm or</p></li><li class="elsevierStyleListItem" id="lsti0585"><span class="elsevierStyleLabel">-</span><p id="par1110" class="elsevierStylePara elsevierViewall">Supradiaphragmatic lymph node involvement plus splenic involvement</p></li></ul></p> <p id="par1115" class="elsevierStylePara elsevierViewall">Stage IV<ul class="elsevierStyleList" id="lis0090"><li class="elsevierStyleListItem" id="lsti0590"><span class="elsevierStyleLabel">-</span><p id="par1120" class="elsevierStylePara elsevierViewall">Non-contiguous extranodal involvement</p></li></ul></p>"
            "etiqueta" => "Appendix 3"
            "titulo" => "Staging of lymphomas according to the Lugano classification"
            "identificador" => "sec0320"
          ]
        ]
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Strength of recommendation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Solid&#44; it must be offered in all situations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&#44; it should be offered regularly&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Optional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">It should generally NOT be offered&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">E&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">It should never be offered&nbsp;\t\t\t\t\t\t\n
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Quality of the findings on which the recommendation is based&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">At least one randomized trial with clinical assessment criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Non-randomized clinical trials&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Expert opinion&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Clinical practice classification of the United States Public Health Service&#47;Infectious Diseases Society of America &#40;USPHS&#47;IDSA&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">CMV&#58; cytomegalovirus&#59; CSF&#58; cerebrospinal fluid&#59; LDH&#58; lactate dehydrogenase&#59; PET&#58; positron emission tomography&#59; MRI&#58; magnetic resonance imaging&#59; CT&#58; computed tomography&#59; HBV&#58; hepatitis B virus&#59; HCV&#58; hepatitis C virus&#59; HIV&#58; human immunodeficiency virus&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History-taking &#40;Anamnesis&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B Signs &#40;any of the following&#41;<br>Fever<br>Night sweats<br>Weight loss greater than 10&#37; in the last 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Physical examination&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Palpable lymphadenopathies &#40;number&#44; size and site&#41;<br>Hepatomegaly and splenomegaly<br>Palpable or visible masses or nodules<br>Waldeyer&#39;s Ring examination&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lab tests&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hematimetry<br>Biochemical tests with determination of LDH&#44; &#946;-2 microglobulin&#44; transaminases&#44; bilirubin&#44; calcium&#44; uric acid&#44; serum proteins&#44; immunoglobulins and immunofixation<br>Serologies&#58; VHB&#44; HCV&#44; CMV&#44; EBV&#44; <span class="elsevierStyleItalic">Toxoplasma</span> and varicella-zoster<br>Plasma viral load of HIV<br>T-lymphocytes subpopulations &#40;CD4&#43; and CD8&#43;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Histology and cytology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Biopsy and bone marrow aspirate<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><br>CSF cytocentrifugation test &#40;conventional cytology and flow cytometry&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Imaging techniques&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chest X-ray<br>Full-body PET-CT<br>Occasionally&#58; ultrasound&#44; MRI&#44; endoscopy or other imaging studies depending on the site of the lymphoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">The usefulness of bone marrow biopsy is under discussion in many cases&#44; as PET shows greater sensitivity in the detection of spinal cord involvement&#46; Currently&#44; Hodgkin&#39;s lymphoma is only performed in cases of high suspicion of infiltration and negative PET&#44; including peripheral cytopenia&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Diagnosis of extension of systemic NHL in HIV-infected patients&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Variables</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Age &#40;&#60;60 years versus &#8805;60 years&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Ann Arbor Stage &#40;I&#8211;II versus III&#8211;IV&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Number of affected extranodal areas &#40;0&#8211;1 versus &#8805;2&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Functional capacity according to ECOG score &#40;1&#8211;2 versus &#8805;2&#41; &#40;ECOG assessment&#58; 0&#58; normal activity&#44; 1&#58; symptomatic&#44; but with normal activity&#44; 2&#58; in bed less than 50&#37; of the time&#44; 3&#58; in bed more than 50&#37; of the time&#44; 4&#58; bed-bound 100&#37; of the time&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Serum LDH &#40;normal versus elevated&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Risk groups</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Assigning a score 0&#8211;1 to each variable of those described&#44; 4 risk groups are defined&#58;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Low risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IPI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#8211;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Intermediate&#47;low risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IPI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Intermediate&#47;high risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IPI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>High risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IPI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#8211;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">International Prognostic Index &#40;IPI&#41; for diffuse large B-cell lymphomas&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Gy&#58; grays&#59; IMRT&#58; intensity modulated radiotherapy&#59; ISRT&#58; involved site radiotherapy&#59; BL&#58; Burkitt&#39;s lymphoma&#59; DLBCL&#58; diffuse large cell B lymphoma&#59; CT&#58; chemotherapy&#59; RT&#58; radiotherapy&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Systemic non-Hodgkin&#39;s lymphomas</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Adjuvant RT after CT stages I and II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Lymphoma where indicated&#58; DLBCL and BL if there is no response to CT&#44; plasmablastic lymphoma in residual masses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Volume&#58; affected lymph node areas &#40;ISRT&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Total doses&#58; 36&#8211;40<span class="elsevierStyleHsp" style=""></span>Gy in fractions of 2<span class="elsevierStyleHsp" style=""></span>Gy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Evidence class&#58; IA</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Primary central nervous system lymphoma</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Volume&#58; holocranial 45<span class="elsevierStyleHsp" style=""></span>Gy in 25 fractions of 1&#46;8<span class="elsevierStyleHsp" style=""></span>Gy without boost with conventional 3<span class="elsevierStyleHsp" style=""></span>D techniques or using IMRT to avoid irradiation of the hippocampi&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Evidence class IA</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Eye involvement&#58; irradiate the entire orbit&#44; better with stereotactic techniques&#46; Lower doses of 31<span class="elsevierStyleHsp" style=""></span>Gy reduce the possibility of brain control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Evidence class&#58; IIB</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Hodgkin&#39;s lymphoma</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Favourable disease &#40;EIA&#44; IIA with less than 3 lymph node areas affected&#41;&#44; RT 20<span class="elsevierStyleHsp" style=""></span>Gy in 10 fractions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Favourable disease IIA without bulky disease&#44; but &#60;4 affected lymph node areas&#58; ISRT 30<span class="elsevierStyleHsp" style=""></span>Gy in 15 fractions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Unfavourable disease with poor response to CT&#58; ISRT dose of 36&#8211;40<span class="elsevierStyleHsp" style=""></span>Gy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Evidence class&#58; IA</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Palliative radiotherapy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Indications&#58; in all cases in which there is uncontrolled pain&#44; compression of adjacent structures&#44; spinal cord compression&#44; bleeding or lack of effectiveness of CT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Dosage 30<span class="elsevierStyleHsp" style=""></span>Gy&#44; 10 fractions of 3<span class="elsevierStyleHsp" style=""></span>Gy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Evidence class&#58; IA</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1805605.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Treatment with radiotherapy in patients with lymphoma associated with HIV infection&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">BURKIMAB&#58; rituximab&#44; methotrexate&#44; dexamethasone&#44; ifosfamide&#44; vincristine&#44; etoposide&#44; cytarabine&#44; doxorubicin and vindesine&#59; CODOX-M&#58; cyclophosphamide&#44; adriamycin&#44; vincristine and methotrexate&#59; CVAD&#58; hyperfractionated cyclophosphamide&#44; vincristine&#44; doxorubicin and dexamethasone&#59; EPOCH&#58; etoposide&#44; prednisone&#44; vincristine&#44; cyclophosphamide&#44; and doxorubicin hydrochloride&#59; G-CSF&#58; granulocyte colony stimulation factor&#59; IVAC&#58; ifosfamide&#44; etoposide and cytarabine&#59; BL&#58; Burkitt&#39;s lymphoma&#59; R-CHOP&#58; rituximab-cyclophosphamide&#44; adriamycin&#44; vincristine and prednisone&#59; RT&#58; radiotherapy&#59; cART&#58; combination antiretroviral treatment&#59; HIV&#58; human immunodeficiency virus&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Antitumor treatment</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Diffuse large B-cell lymphoma</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Stage IA and IIA&#58; R-CHOP &#40;3 cycles&#41; administered every 21 days<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>ISRT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Other stages&#58; 6 cycles of R-CHOP administered every 21 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Burkitt&#39;s syndrome</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>CODOX-M&#47;IVAC or similar regimens &#40;HyperCVAD or BURKIMAB&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Add rituximab to all previous regimens&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>In patients with significant comorbidity EPOCH can be used&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Aggressive B-cell disease with</span> MYC <span class="elsevierStyleItalic">and</span> BCL2 <span class="elsevierStyleItalic">and&#47;or</span> BCL6 gene rearrangement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Chemotherapy regimens designed for BL&#44; with rituximab&#46; AD-EPOCH-R can be used as an alternative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:1.0px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Antiretroviral treatment</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">If the patient is receiving cART&#44; keep it adapted to the treatment of the lymphoma</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">If the patient is without cART&#44; initiate it together with the lymphoma treatment</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:1.0px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Support and complementary treatment in all cases</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Tumour lysis syndrome prophylaxis &#40;1st cycle&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Meningeal prophylaxis &#40;see text&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Opportunistic infections prophylaxis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Use of G-CSF</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1805601.png"
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Overview of the treatment of non-Hodgkin&#39;s lymphomas associated with HIV infection&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at6"
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        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">This system includes 7 factors&#44; each of which reduces the probability of disease control at 5 years &#40;see text&#41;&#46;</p>"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age over 45 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Haemoglobin<span class="elsevierStyleHsp" style=""></span>&#8810;<span class="elsevierStyleHsp" style=""></span>10&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Leukocytes<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1&#46;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lymphocytes<span class="elsevierStyleHsp" style=""></span>&#8810;<span class="elsevierStyleHsp" style=""></span>0&#46;6<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage <span class="elsevierStyleItalic">IV</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Hasenclever Prognostic Index for Advanced Hodgkin Disease&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0035"
        "etiqueta" => "Table 7"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
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            "detalle" => "Table "
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">ABVD&#58; adriamycin&#44; bleomycin&#44; vinblastine&#44; dacarbazine&#59; BEACOPP&#58; bleomycin&#44; etoposide&#44; adriamycin&#44; cyclophosphamide&#44; vincristine&#44; procarbazine&#44; prednisone&#59; ESHAP&#58; etoposide&#44; methylprednisolone&#44; cytarabine&#44; cisplatin&#59; ICE&#58; ifosfamide&#44; etoposide&#44; carboplatin&#59; HL&#58; Hodgkin&#39;s lymphoma&#59; PET&#58; positron emission tomography&#59; HSCT&#58; hematopoietic stem cell transplantation&#59; HIV&#58; human immunodeficiency virus&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Initial stages with good prognosis criteria</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ABVD chemotherapy</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#215;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">2</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#43;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">radiotherapy &#40;see below&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">As an alternative&#44; ABVD chemotherapy</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#215;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">4 &#40;control with PET during treatment&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Initial stages with poor prognosis criteria</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ABVD chemotherapy</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#215;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">4</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#43;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Radiotherapy &#40;see below&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Alternatives</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ABVD chemotherapy<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>6 &#40;control with PET during treatment&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Chemotherapy BEACOPP<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>ABVD<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Radiotherapy &#40;see below&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Advanced stages</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ABVD chemotherapy</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#215;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">6 and consider radiotherapy on residual masses</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Alternative&#58; BEACOPP chemotherapy</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#215;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Relapse of HL</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Second line chemotherapy&#58; ESHAP&#44; DHAP&#44; ICE and consolidation with autologous HSCT &#40;exceptionally allogeneic HSCT&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">In patients with refractory or relapse HL after autologous HSCT&#58; brentuximab&#44; PD-1&#47;PDL-1 inhibitors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Practical recommendations for the treatment of Hodgkin&#39;s lymphoma in HIV-infected population&#46;</p>"
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      ]
      7 => array:8 [
        "identificador" => "tbl0040"
        "etiqueta" => "Table 8"
        "tipo" => "MULTIMEDIATABLA"
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            "identificador" => "at8"
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">HL&#58; Hodgkin&#39;s lymphoma&#59; NHL&#58; non-Hodgkin&#39;s lymphomas&#59; CR&#58; complete remission&#59; cART&#58; potent combination antiretroviral treatment&#59; HIV&#58; human immunodeficiency virus&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Inclusion criteria &#40;all three must be met&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">1&#46; NHL or HL in any of the following situations</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>After the second CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>After the first CR when more than one line of chemotherapy was required&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>After partial remission of the lymphoma when the tumour is considered sensitive to chemotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">2&#46; Good general condition</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Without active AIDS-defining infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Absence of serious diseases &#40;e&#46;g&#46;&#44; liver cirrhosis&#44; advanced heart disease&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">3&#46; Good control of HIV infection with cART</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>It should not be offered to patients in situation of virologic failure without rescue option&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Therapeutic procedure</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Administration of high doses of chemotherapy&#44; followed by the infusion of hematopoietic stem cells obtained from peripheral blood of the same patient</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">The joint opinion of haematologists or oncologists and specialists in HIV infection is required&#46;</p>"
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            1 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">The informed consent of the patient is required&#46;</p>"
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Autologous transplants of hematopoietic stem cell in patients with lymphomas and HIV infection&#46;</p>"
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