Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy

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Supervivencia global de los pacientes tratados con R-CHOP: comparación de LT con LDCBG de novo. B. 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Age-adjusted by the direct method, using the age group distribution of the 2003 SNHS participants: 16–39 years, 40–59 years and ≥60 years." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Francisco Javier Basterra-Gortari, Maira Bes-Rastrollo, Miguel Ruiz-Canela, Alfredo Gea, Miguel Ángel Martinez-Gonzalez" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Francisco Javier" "apellidos" => "Basterra-Gortari" ] 1 => array:2 [ "nombre" => "Maira" "apellidos" => "Bes-Rastrollo" ] 2 => array:2 [ "nombre" => "Miguel" "apellidos" => "Ruiz-Canela" ] 3 => array:2 [ "nombre" => "Alfredo" "apellidos" => "Gea" ] 4 => array:2 [ "nombre" => "Miguel Ángel" "apellidos" => "Martinez-Gonzalez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775316306364" "doi" => "10.1016/j.medcli.2016.11.022" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775316306364?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020617301845?idApp=UINPBA00004N" "url" => "/23870206/0000014800000006/v1_201704120030/S2387020617301845/v1_201704120030/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "243" "paginaFinal" => "249" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Marc Sorigue, Olga Garcia, Maria Joao Baptista, Juan-Manuel Sancho, Gustavo Tapia, José Luis Mate, Evarist Feliu, José-Tomás Navarro, Josep-Maria Ribera" "autores" => array:9 [ 0 => array:3 [ "nombre" => "Marc" "apellidos" => "Sorigue" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Olga" "apellidos" => "Garcia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Maria Joao" "apellidos" => "Baptista" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Juan-Manuel" "apellidos" => "Sancho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Gustavo" "apellidos" => "Tapia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "José Luis" "apellidos" => "Mate" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 6 => array:3 [ "nombre" => "Evarist" "apellidos" => "Feliu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 7 => array:4 [ "nombre" => "José-Tomás" "apellidos" => "Navarro" "email" => array:1 [ 0 => "jnavarro@iconcologia.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 8 => array:3 [ "nombre" => "Josep-Maria" "apellidos" => "Ribera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Hematología, Hospital ICO-Germans Trias i Pujol, Instituto de Investigación contra la Leucemia Josep Carreras, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Patología, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Pronóstico similar de los linfomas transformados y los linfomas difusos de células B grandes de novo en pacientes tratados con inmunoquimioterapia" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2499 "Ancho" => 1555 "Tamanyo" => 188269 ] ] "descripcion" => array:1 [ "en" => "(A) Overall survival of the patients with TL compared with de novo DLBCL. (B) Progression free survival of the patients with TL compared with de novo DLBCL." ] ] ] "textoCompleto" => "IntroductionDiffuse large B-cell lymphomas (DLBCL) transformed from low-grade lymphoproliferative neoplasms (TL) have historically been associated with an aggressive course and poor prognosis.<a class="elsevierStyleCrossRefs" href="#bib0180">1,2</a> Nonetheless, some studies in the immunochemotherapy era have reported an improvement in the prognosis of these neoplasms.<a class="elsevierStyleCrossRefs" href="#bib0190">3–5</a>In the pre-rituximab era several studies showed a markedly better prognosis in TL patients receiving consolidation treatment with high-dose chemotherapy and autologous stem cell transplantation (ASCT) than those receiving only chemotherapy.<a class="elsevierStyleCrossRefs" href="#bib0205">6,7</a> However, following the introduction of rituximab the survival of patients with TL has improved, being similar to that of de novo DLBCL, regardless of the administration of consolidation chemotherapy and ASCT.<a class="elsevierStyleCrossRefs" href="#bib0195">4,8,9</a>Although most TL studies have focused on transformation from follicular lymphoma (FL) (2–3% per year),<a class="elsevierStyleCrossRefs" href="#bib0180">1,2,8</a> other indolent lymphoproliferative neoplasms, such as marginal zone lymphoma (MZL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), can also transform into DLBCL. The frequency of transformation from MZL, including splenic MZL and nodal MZL, into DLBCL ranges between 5% and 10%,<a class="elsevierStyleCrossRefs" href="#bib0225">10–12</a> with scarce data available on its prognosis in the rituximab era.<a class="elsevierStyleCrossRef" href="#bib0240">13</a> Of note, there are reports of selected gastric MALT cases evolving to DLBCL<a class="elsevierStyleCrossRef" href="#bib0245">14</a> successfully treated with only eradication treatment of Helicobacter pylori by antibiotics. Conversely, it is well known that Richter syndrome (transformation of CLL into a high-grade lymphoma) responds poorly to treatment and entails a particularly bad prognosis.<a class="elsevierStyleCrossRef" href="#bib0250">15</a>The pathobiological characteristics and clinical outcome of DLBCL are heterogeneous with 3 major groups correlated with outcome having been identified according to their cell-of-origin (COO) by gene expression profiling (GEP): germinal center B-cell-like (GCB), activated B-cell-like (ABC), and unclassified.<a class="elsevierStyleCrossRef" href="#bib0255">16</a> Several algorithms have been developed using immunohistochemical markers in an attempt to reproduce the GEP results and establish the COO using more readily available technology. The Hans algorithm is most commonly used and it classifies DLBCL into GCB and non-GCB. With this method, some groups have identified the COO as an independent prognostic factor for survival in DLBCL,<a class="elsevierStyleCrossRefs" href="#bib0260">17–18</a> while others have not.<a class="elsevierStyleCrossRefs" href="#bib0270">19,20</a> To our knowledge, in the rituximab era few studies have analyzed both the survival and the prognostic influence of the COO in TL, particularly TL from low-grade lymphomas other than FL.Therefore, in the present study we compared the clinical and biological features (including the COO) as well as the prognosis of TL and de novo DLBCL treated with immunochemotherapy in a single institution.Patients and methodsPatientsThe records of 163 consecutive de novo DLBCL and 31 TL diagnosed from 2003 to 2012 in our institution were reviewed. Only patients treated with immunochemotherapy were selected. In all cases, the diagnosis was made by tissue biopsy. Patients with HIV-infection, those from whom a biopsy specimen was unavailable for revision and patients with specific subtypes of DLBCL such as primary cutaneous DLBCL, primary central nervous system lymphoma or primary mediastinal DLBCL, were excluded from the study.The main clinical and biological data were collected, as were the treatment and outcome of both the prior low-grade and the high-grade lymphoma. The COO was established by means of the Hans algorithm, which uses the imunohistochemical expression of CD10, BCL6 and MUM1 on formalin-fixed-paraffin-embedded tissue sections to classify DLBCL into GCB and non-GCB.<a class="elsevierStyleCrossRef" href="#bib0260">17</a>TL was defined as biopsy-proven DLBCL in patients with a previous diagnosis of a low-grade lymphoproliferative disorder (FL, CLL, MZL) or as cases with both DLBCL and a low-grade lymphoproliferative disorder diagnosed at the same time (in the same or another lymph node). This latter situation, known as composite lymphoma, is often considered TL at diagnosis,<a class="elsevierStyleCrossRefs" href="#bib0205">6,20,21</a> based on the molecular evidence of a clonal relationship between DLBCL and FL.<a class="elsevierStyleCrossRefs" href="#bib0285">22,23</a> The study received institutional approval by the ethical committee of Germans Trias I Pujol Hospital (code LT2015).Statistical analysisBaseline demographic and clinical and biological characteristics are presented as median and range for continuous variables and frequency and percentage for categorical variables. Comparisons of these variables between patient groups were performed by the χ2, the Fisher's exact, Student's-t or Mann–Whitney's U test, as appropriate.Complete response criteria were according to previously reported.<a class="elsevierStyleCrossRef" href="#bib0295">24</a> Time to transformation (TTT) was defined as the time interval between the diagnosis of the low-grade lymphoma and the diagnosis of TL. Progression-free survival (PFS) was defined as the time from diagnosis to relapse, progression or death due to any cause. Overall survival (OS) was defined as the time from diagnosis to the time of death by any cause.<a class="elsevierStyleCrossRef" href="#bib0295">24</a>The Kaplan–Meier method was used to calculate the OS and PFS curves, and the log-rank test was used to compare the survival between groups (TL and de novo DLBCL). The variables that showed a difference between the two groups with a p value <0.2, and were considered clinically relevant, were also included to perform the multivariate analyses using Cox's proportional hazards regression model. All these studies were performed using SPSS v15.0 software (IBM, Somer, NY).ResultsPatientsOf 163 patients with de novo DLBCL, 22 were excluded because of HIV-positive status and 29 because the diagnostic tissue sample was not available for revission. Three patients with primary cutaneous DLBCL leg type, 2 with primary mediastinal DLBCL and 6 patients not treated with immunochemotherapy (including 4 primary CNS lymphomas) were also excluded from the study. Of 31 TL, 2 patients were excluded because they were not treated with immunochemotherapy. One-hundred and one de novo DLBCL and 29 TL were finally included in the study. Of the 29 TL, 10 were composite lymphomas (considered as TL at diagnosis), 9 had a previous diagnosis of FL, 6 of MZL and 4 of CLL. As shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, there were no differences between the two groups, other than CD10-positivity. International prognostic index (IPI), a score that encompasses the most important clinical and analytical prognostic variables and which defines broadly different prognostic groups, did not differ between TL and de novo DLBCL. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the clinical and analytical features depending on the low grade lymphoma.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Cell of originImmunohistochemical data for assessing the COO was available in 23 of 29 TL and in 76 of 101 de novo DLBCL. All TL evolving from FL (7/7) and all composite lymphomas (9/9) were GCB, while all TL from MZL (4/4) and from CLL (3/3) were non-GCB. Thirty-two de novo DLBCL were GCB while 44 were non-GCB. Overall, CD10 was expressed more frequently in TL tissue than in de novo DLBCL (67% vs. 30%, p=0.002); consequently, TL was more frequently GCB (16 of 23 [70%]) than de novo DLBCL (32 of 76 [42%]) (p=0.031) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).Treatment and outcome of the low-grade lymphoma before transformationTen patients with low-grade lymphomas were treated with immunochemotherapy, including 6 FL, 3 MZL and 1 CLL. Five cases received R-CHOP, 3 R-CVP, 1 R-FCM (rituximab, fludarabine, cyclophosphamide and mitoxantrone) and the remaining patient underwent splenectomy followed by rituximab and chlorambucil. None of these patients received maintenance with rituximab. Nine patients (3 FL, 3 MZL, 3 CLL) did not receive rituximab at all: 4 patients who did not receive any treatment before transformation, 2 cases treated only with surgery, and 3 who received chemotherapy without rituximab. Ten were composite lymphomas and hence considered as TL at diagnosis.Patients who received immunochemotherapy for the low-grade lymphoma (No.=10) transformed at a median of 3.6 years (range: 0.6–6.6) after the initial diagnosis, while those that did not (No.=9), transformed after a median of 2.6 years (range: 0.4–22). The 5-year OS probability for these two groups after transformation was 50% (95%CI: 19%-81%) and 60% (95%CI: 24%-96%), respectively (p=0.110).Treatment and outcome of the high-grade lymphoma (TL and de novo DLBCL)Twenty patients with TL were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). Other immunochemotherapy regimens used were R-ESHAP (rituximab, etoposide, cisplatin, cytarabine and prednisone [5 cases]), R-CVP (rituximab, cyclophosphamide, vincristine and prednisone [3 cases]) and R-GEMOX (rituximab, gemcitabine, cisplatin [1 case]). Four patients received radiotherapy (RDT) as part of the first line treatment. Five TL cases received consolidation with high-dose chemotherapy and ASCT (4 after R-CHOP) and 2 with allogeneic stem cell transplantation after achieving the first complete response (CR). Ninety-one patients with de novo DLBCL were treated with R-CHOP. Other regimens used were R-CVP (6 cases) and EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab) in 2 cases and dose-intensive chemotherapy including rituximab and high-dose methotrexate and cytarabine<a class="elsevierStyleCrossRef" href="#bib0300">25</a> in 2 cases. Twenty-seven patients received RDT. No patient with de novo DLBCL received stem cell transplantation in first CR.There were no differences in the CR rate between TL (18 of 29) and de novo DLBCL (66 of 101) after the first line therapy (62% vs 66%, p=0.825). Furthermore, there were no differences in OS or in PFS (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), with a median follow-up of 4.5 years. Multivariate analyses for OS and PFS of the whole series including TL, Ann-Arbor stages III/IV and bone marrow infiltration as unfavorable factors, showed a lack of prognostic impact on survival in any of them.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>There were no differences between GCB TL and GCB de novo DLBCL or in OS (5yr. OS [95% CI]: 62% [38%-86%] vs. 63% [44%-82%], p=0.850) or PFS (5 yr. PFS: 42% [17%-67%] vs. 60% [41%-79%], p=0.204).Patients treated with R-CHOP without transplantation in CR (14 patients in the TL group and 76 in the de novo DLBCL group) were analyzed separately. Again, there were no differences in 5-year OS or PFS probabilities between TL and de novo DLBCL (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), even though the groups were no longer similar in terms of stage at diagnosis (the TL group had a higher percentage of cases presenting in advanced stages [<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>]).<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>In the multivariate analyses restricted to patients who received R-CHOP, without SCT consolidation, advanced stage was an adverse prognostic factor for OS (and a trend for PFS) while TL was not an unfavorable factor for either OS or for PFS (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Only one out of the 7 patients who received SCT (5 ASCT and 2 allogeneic) as first line treatment (all in the TL group) had an advanced stage at diagnosis of TL, while 5 presented with localized disease and the information was not available in the remaining patient. All 5 patients treated with ASCT were alive at the time of data collection; 4 were in CR while the remaining patient was in partial response. The 2 patients who received allogeneic stem cell transplantation, in spite of CR died of infectious complications, 1 and 4 years after transplantation.At the time of data collection, 13 patients with TL had died; 10 due to lymphoma progression and 3 due to infection, including the two patients who received allogeneic stem cell transplantation. In the de novo DLBCL group, 33 patients had died, 20 due to lymphoma progression, 8 due to infection, and 5 due to other multiple causes unrelated to the disease or the treatment.DiscussionIn the present study, patients with TL treated with immunochemotherapy seemed to have a similar CR rate and 5-year OS and PFS probability as those with de novo DLBCL. Despite the limitations of the study, these findings reflect an improvement in the prognosis of TL treated with immunochemotherapy compared to the pre-rituximab era.<a class="elsevierStyleCrossRefs" href="#bib0180">1,2</a> The demographic and clinical characteristics were similar in both groups. Regarding the biological features of the tumor, the data show that the COO of TL is dependent on the low-grade lymphoma from which it evolves. TL from MZL and CLL were non-GCB in all cases, while all TL from FL were GCB. In our series, TL were more frequently GCB because it most often transformed from FL or was diagnosed synchronously with this lymphoma, as shown in other series.<a class="elsevierStyleCrossRefs" href="#bib0220">9,20,26</a> To our knowledge, this issue has not been analyzed for TL derived from lymphoproliferative neoplasms other than FL, and our data show that the COO was non-GCB in these cases.The similar outcomes of patients with TL and de novo DLBCL found in our series are in agreement the results of other authors.<a class="elsevierStyleCrossRefs" href="#bib0190">3–5,8,9</a> Since the introduction of rituximab for the treatment of CD20-positive lymphomas, the prognosis of TL has improved.<a class="elsevierStyleCrossRefs" href="#bib0180">1,2</a> A recent large prospective study including patients with FL showed a 5-year OS probability of 75% after transformation, a notable improvement over those obtained before immunochemotherapy27. This study also showed a slightly worse prognosis in patients with DLBCL diagnosed after the diagnosis of FL compared to those diagnosed simultaneously, a result that we could not examine in our series due to the small size of the groups. Concerning the GCB subgroup, there were no differences in the prognosis between TL and de novo DLBCL. Unfortunately, the small sample size of the non-GCB TL did not allow to compare the outcomes of these patients and those of the non-GCB de novo DLBCL patients. As the non-GCB origin is known to carry a worse prognosis, at least in de novo DLBCL, larger series are needed in order to establish whether the prognosis of non-GCB TL is also similar to that of non-GCB de novo DLBCL treated with immunochemotherapy. Furthermore, we found a similar OS and PFS in TL and de novo DLBCL taking into account only patients treated with R-CHOP without SCT. A large, recently published series, including de novo DLBCL and TL treated with R-CHOP showed the same conclusion.<a class="elsevierStyleCrossRef" href="#bib0200">5</a> Interestingly, despite having similar outcomes, TL patients from our series were more likely to present in advanced stage, which on multivariate analysis was the only adverse risk factor found, in accordance with previous studies in patients with TL.<a class="elsevierStyleCrossRefs" href="#bib0185">2,28</a> These data, together with those from other series,<a class="elsevierStyleCrossRefs" href="#bib0195">4,5,29</a> suggest that consolidation with ASCT after R-CHOP is not needed in patients with TL. Several studies have shown a favorable effect of consolidation with ASCT for the treatment of TL. However, these studies were biased in that patients not undergoing ASCT most often had chemo-resistant or progressive disease, had comorbidities, worse performance status or were unable to mobilize enough stem cells for the procedure.<a class="elsevierStyleCrossRefs" href="#bib0195">4,30</a> In our study only 1 patient receiving ASCT presented with advanced stage at diagnosis of TL, which confirms that patients with better baseline conditions and/or a less aggressive disease undergo ASCT. This selection bias makes difficult to assess the real benefits that ASCT may have in this population. On the other hand, no study to date has shown that patients do not benefit from ASCT. Other post-induction strategies, such as rituximab maintenance or consolidation with radioimmunotherapy, could also be considered in certain patients, as these patients may still have a low-grade component. In fact, a recent retrospective series found consolidation with radioimmunotherapy to be an efficacious strategy in patients with TL that were not eligible for ASCT.<a class="elsevierStyleCrossRef" href="#bib0330">31</a>The most frequent cause of death of patients with TL was lymphoma progression. On the other hand, the two patients who received allogeneic stem cell transplantation ultimately died of sepsis while in CR. Despite the small sample size, similar results have been described in the literature,<a class="elsevierStyleCrossRef" href="#bib0335">32</a> indicating that allogeneic SCT is very effective for the control of the disease but carries a very high rate of transplant-related mortality, mainly associated with the immunosuppression and graft-versus-host disease. On the other hand, the outcomes after allogeneic SCT are very variable<a class="elsevierStyleCrossRef" href="#bib0340">33</a> (3-year PFS and OS probabilities of up to 83% and 85%, respectively, have been described<a class="elsevierStyleCrossRef" href="#bib0345">34</a>), depending on both the institution and the patient selection and therefore, it might be an appropriate option for some patients.With regard to the treatment of indolent lymphoma, the addition of rituximab seems to influence the TTT. In our study, the TTT in patients receiving immunochemotherapy for indolent lymphoma was 3.6 years, being 2.6 years in those treated without rituximab. Some studies have found a shorter TTT as well as a more aggressive course of high-grade lymphomas in patients receiving rituximab as part of the treatment for the indolent lymphoma.<a class="elsevierStyleCrossRefs" href="#bib0190">3,30</a> In a large prospective series, treatment of FL with immunochemotherapy was correlated with delayed progression to TL<a class="elsevierStyleCrossRef" href="#bib0215">8</a> and in another one, rituximab maintenance of patients with FL was correlated with a decreased risk of TL.<a class="elsevierStyleCrossRef" href="#bib0310">27</a> In our study, no differences were observed in prognosis after transformation between patients who received rituximab for the indolent lymphoma and those who did not. This lack of differences may be due to the small sample size, since other series analyzing the effect of immunochemotherapy for low-grade lymphoma on the prognosis of TL have described a better prognosis for rituximab-naive patients after transformation.<a class="elsevierStyleCrossRefs" href="#bib0190">3,30</a>One of the limitations of this study is its retrospective nature, which led to pooling heterogeneously-treated patients (importantly, patients treated and not treated with regimens including anthracyclines and patients receiving and not receiving SCT). The limited number of cases did prevent certain analyses to be performed, particularly the potential benefits of undergoing SCT. Similarly, the outcomes of TL from FL could not be compared with those of TL from the CLL and MZL subgroups, which would have been interesting for comparing GCB vs. non-GCB TL. Furthermore, chromosomal rearrangement of the MYC and BCL2 genes, which are known to impact prognosis in de novo DLBCL,<a class="elsevierStyleCrossRef" href="#bib0350">35</a> was not examined in the majority of patients. This would be an essential biological analysis in any prospective study concerning the prognosis of TL.In summary, in this series, although retrospective and heterogeneous, the prognosis of patients with TL and de novo DLBCL treated with immunochemotherapy seems to be similar, especially in those receiving R-CHOP without SCT, in accordance with other reports performed in the rituximab era. The treatment of indolent lymphoma with regimens including rituximab may delay transformation but it does not seem influence on survival.The TL phenotype was GCB on transformation from FL and non-GCB on transformation from MZL and CLL. Further studies including a larger number of patients are needed to determine whether the prognosis of TL from FL is different from that of TL from other indolent lymphomas treated with immunochemotherapy.FundingThis work was funded in part by a grant from the Instituto de Salud Carlos III, Ministerio de Economia y Competividad, Spain, Red Temática de Investigación Cooperativa en Cáncer (RTICC, FEDER) (RD12/0036/0044); 2014 SGR225 (GRE) Generalitat de Catalunya; economical support from Fundació Internacional Josep Carreras. The research leading to this article has received funding from “la Caixa Foundation”.Conflict of interestMJB and JTN received a research grant from CELGENE Spain." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres827180" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec823509" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres827181" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec823510" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0025" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Cell of origin" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Treatment and outcome of the low-grade lymphoma before transformation" ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Treatment and outcome of the high-grade lymphoma (TL and de novo DLBCL)" ] ] ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-03-27" "fechaAceptado" => "2016-09-29" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec823509" "palabras" => array:4 [ 0 => "Transformed lymphoma" 1 => "Immunotherapy" 2 => "Chemotherapy" 3 => "Prognosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec823510" "palabras" => array:4 [ 0 => "Linfoma transformado" 1 => "Inmunoterapia" 2 => "Quimioterapia" 3 => "Pronóstico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundThe prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. Patients and methodsWe compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. ResultsPatients with TL and de novo DLBCL had similar characteristics. All TL cases evolving from follicular lymphoma were germinal-center B-cell-like, while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like. The complete response rate was similar in TL and de novo DLBCL (62 vs. 66%, p=0.825). The 5-year overall and progression-free survival probabilities (95% CI) were 59% (40–78) and 41% (22–60) for TL and 63% (53–73) and 60% (50–70) for de novo DLBCL, respectively (p=0.732 for overall survival and p=0.169 for progression-free survival). ConclusionIn this study, the prognosis of TL and de novo DLBCL treated with immunochemotherapy was similar. The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "AntecedentesEl pronóstico de los linfomas difusos de células B grandes (LDCBG) transformados de linfomas indolentes (LT) ha sido considerado más desfavorable que el pronóstico de LDCBG de novo. Sin embargo, este parece haber mejorado desde la introducción de rituximab. Pacientes y métodosSe compararon las características (incluyendo la célula de origen) y el pronóstico de 29 pacientes con LT y 101 con LDCBG de novo tratados con inmunoquimioterapia. ResultadosLos pacientes con LT y LDCBG de novo tenían características similares. Todos los casos de LT que evolucionaron de un linfoma folicular fueron linfomas de células B de tipo centro germinal, mientras que aquellos LT que evolucionaron de un linfoma de la zona marginal o leucemia linfocítica crónica fueron de tipo no centro germinal. El índice de respuesta completa fue similar en los LT y en los LDCBG de novo (62 frente a 66%, p=0,825). Las probabilidades de supervivencia global y libre de progresión a 5 años (IC 95%) fueron del 59% (40–78) y el 41% (22–60) para LT y del 63% (53–73) y el 60% (50–70) para LDCBG de novo, respectivamente (p=0,732 para supervivencia global y p=0,169 para supervivencia libre de progresión). ConclusiónEn este estudio, el pronóstico de los LT y LDCBG de novo tratados con inmunoquimioterapia fue similar. El papel de la intensificación con trasplante de precursores hematopoyéticos en el tratamiento del LT puede ser cuestionable en la era del rituximab." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Sorigue M, Garcia O, Baptista MJ, Sancho J-M, Tapia G, Mate JL, et al. Pronóstico similar de los linfomas transformados y los linfomas difusos de células B grandes de novo en pacientes tratados con inmunoquimioterapia. Med Clin (Barc). 2017;148:243–249." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2499 "Ancho" => 1555 "Tamanyo" => 188269 ] ] "descripcion" => array:1 [ "en" => "(A) Overall survival of the patients with TL compared with de novo DLBCL. (B) Progression free survival of the patients with TL compared with de novo DLBCL." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2522 "Ancho" => 1559 "Tamanyo" => 186489 ] ] "descripcion" => array:1 [ "en" => "(A) Overall survival of the patients treated with R-CHOP: comparison of TL with de novo DLBCL. (B) Progression free survival of the patients treated with R-CHOP: comparison of TL with de novo DLBCL." ] ] 2 => 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:2 [ "leyenda" => "TL: transformed lymphoma; DLBCL: Diffuse large B-cell lymphoma; LDH: lactate dehydrogenase; IPI: international prognostic index; GCB; germinal center B-cell; COO: cell-of-origin.The results in bold indicate a p with statistical significance." "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=""><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">TL (n=29) \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">DLBCL (n=101) \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">p \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">Total (n=130) \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">Male, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15/29 (52) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51/101 (51) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66/130 (51) \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">Age, median (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 (43, 83) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 (24, 87) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.487 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62 (24, 87) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Stage, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I–II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9/28 (32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47/100 (47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.198 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56/128 (44) \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–IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19/28 (68) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53/100 (53) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72/128 (56) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B symptoms, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8/26 (31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37/101 (37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.651 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45/127 (35) \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">Bone marrow infiltration, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8/28 (29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17/101 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.182 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25/129 (19) \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">Extranodal disease, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13/28 (46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36/101 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.379 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49/129 (38) \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 extranodal areas, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3/28 (11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17/101 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.562 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20/129 (16) \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 serum LDH, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11/25 (44) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49/94 (52) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.507 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60/119 (50) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">IPI, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Low (0–1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7/25 (28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33/93 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.707 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40/118 (34) \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">Low/Int (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10/25 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26/93 (28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36/118 (31) \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/Int (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5/25 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19/93 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24/118 (20) \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 (4–5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3/25 (12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15/93 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18/118 (15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CD10-positive, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16/24 (67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27/89 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43/113 (38) \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">BCL6-positive, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20/23 (87) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75/94 (80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.559 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95/117 (81) \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">MUM1-positive, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10/12 (83) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50/66 (76) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.772 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60/78 (77) \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">GCB COO, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16/23 (70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32/76 (42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.031 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48/99 (48) \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">Median follow-up, years (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.1 (0.8, 10.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.1 (0.1, 10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.5 (0.1, 10.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1391518.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Baseline characteristics of the patients with TL and de novo DLBCL." ] ] 3 => 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:2 [ "leyenda" => "LDH: lactate dehydrogenase; IPI: international prognostic index; GCB: germinal center B-cell; COO: cell-of-origin; FL: Follicular lymphoma; CL: composite lymphoma; MZL: marginal zone lymphoma; CLL: chronic lymphocytic leukemia." "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=""><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">FL (n=19) \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">MZL (n=6) \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">CLL (n=4) \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">Male, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10/19 (53) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3/6 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/4 (50) \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">Age, median (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 (43, 83) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 (47, 71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57 (51, 64) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">Stage, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I–II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4/18 (22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/6 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3/4(75) \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–IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14/18 (78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4/6 (67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1/4 (25) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B symptoms, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6/17 (35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0/6 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/3 (67) \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">Bone marrow infiltration, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7/18 (39) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1/6 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0/4 (0) \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">Extranodal disease, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9/18 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/6 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/4 (50) \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 extranodal areas, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/18 (11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1/6 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0/4 (0) \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 serum LDH, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6/16 (38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5/6 (83) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0/4 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">IPI, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Low (0–1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4/16 (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1/6 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/3 (67) \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">Low/Int (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7/16 (44) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/6 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1/3 (33) \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/Int (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3/16 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/6 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0/3 (0) \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 (4–5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/16 (12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1/6 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0/3 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CD10-positive, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16/16 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0/5 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0/3 (0) \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">BCL6-positive, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15/16 (94) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3/4 (75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/3 (67) \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">MUM1-positive, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4/6 (67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4/4 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/2 (100) \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">GCB COO, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16/16 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0/4 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0/3 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1391519.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Baseline characteristics of TL patients according to the type of low grade lymphoma." ] ] 4 => 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:2 [ "leyenda" => "TL: transformed lymphoma; DLBCL: Diffuse large B-cell lymphoma; SCT: stem cell transplantation; LDH: lactate dehydrogenase; IPI: international prognostic index; COO: cell-of-origin.The results in bold indicate a p with statistical significance." "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=""><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">TL (n=14) \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">DLBCL (n=76) \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">p \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">Male, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6/14 (43) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37/76 (49) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.776 \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">Age, median (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 (43, 72) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61 (24, 83) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.840 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">Stage, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I–II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/14 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36/75 (48) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.036 \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–IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12/14 (86) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39/75 (52) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B symptoms, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3/13 (23) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29/76 (38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.363 \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">Bone marrow infiltration, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4/14 (29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12/76 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.264 \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">Extranodal disease, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5/14 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25/76 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">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">≥2 extranodals areas, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/14 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12/76 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">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">High serum LDH, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5/12 (42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35/69 (51) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.756 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">IPI, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Low (0–1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2/12 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26/68 (38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" 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">Low/Int (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5/12 (42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23/68 (34) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" 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">High/Int (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4/12 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11/68 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" 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">High (4–5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1/12 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8/68 (12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CD10-positive, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9/12 (75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20/65 (31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.007 \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">BCL6-positive, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12/12 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55/69 (80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.114 \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">MUM1-positive, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3/4 (75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34/49 (69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \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">COO: GCB, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9/12 (75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25/56 (45) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.109 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1391517.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Baseline characteristics of the patients with TL and de novo DLBCL treated with R-CHOP without SCT consolidation." ] ] 5 => 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" => "TL: transformed lymphoma; OS: Five-year overall survival; PFS: Five-year progression-free survival.The results in bold indicate a p with statistical significance." "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=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Unfavorable group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">OS</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">PFS</th></tr><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="" 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">HR (CI 95%) \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">p \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">HR (CI 95%) \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">p \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">TL vs. de novo DLBCL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7 (0.3, 2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.545 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.2 (0.5, 2.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.633 \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">Ann Arbor stage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III–IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.5 (1.1, 5.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.035 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.9 (0.9, 4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.098 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1391520.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Multivariate analyses of patients treated with RCHOP (without SCT consolidation)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:35 [ 0 => array:3 [ "identificador" => "bib0180" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. 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Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy

Pronóstico similar de los linfomas transformados y los linfomas difusos de células B grandes de novo en pacientes tratados con inmunoquimioterapia

Marc Soriguea, Olga Garciaa, Maria Joao Baptistaa, Juan-Manuel Sanchoa, Gustavo Tapiab, José Luis Mateb, Evarist Feliua, José-Tomás Navarroa,

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jnavarro@iconcologia.net

Corresponding author.

, Josep-Maria Riberaa

a Departamento de Hematología, Hospital ICO-Germans Trias i Pujol, Instituto de Investigación contra la Leucemia Josep Carreras, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain

b Departamento de Patología, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Diffuse large B-cell lymphomas &#40;DLBCL&#41; transformed from low-grade lymphoproliferative neoplasms &#40;TL&#41; have historically been associated with an aggressive course and poor prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">1&#44;2</span></a> Nonetheless&#44; some studies in the immunochemotherapy era have reported an improvement in the prognosis of these neoplasms&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">3&#8211;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In the pre-rituximab era several studies showed a markedly better prognosis in TL patients receiving consolidation treatment with high-dose chemotherapy and autologous stem cell transplantation &#40;ASCT&#41; than those receiving only chemotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">6&#44;7</span></a> However&#44; following the introduction of rituximab the survival of patients with TL has improved&#44; being similar to that of <span class="elsevierStyleItalic">de novo</span> DLBCL&#44; regardless of the administration of consolidation chemotherapy and ASCT&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">4&#44;8&#44;9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although most TL studies have focused on transformation from follicular lymphoma &#40;FL&#41; &#40;2&#8211;3&#37; per year&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">1&#44;2&#44;8</span></a> other indolent lymphoproliferative neoplasms&#44; such as marginal zone lymphoma &#40;MZL&#41; and chronic lymphocytic leukemia&#47;small lymphocytic lymphoma &#40;CLL&#47;SLL&#41;&#44; can also transform into DLBCL&#46; The frequency of transformation from MZL&#44; including splenic MZL and nodal MZL&#44; into DLBCL ranges between 5&#37; and 10&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">10&#8211;12</span></a> with scarce data available on its prognosis in the rituximab era&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">13</span></a> Of note&#44; there are reports of selected gastric MALT cases evolving to DLBCL<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">14</span></a> successfully treated with only eradication treatment of Helicobacter pylori by antibiotics&#46; Conversely&#44; it is well known that Richter syndrome &#40;transformation of CLL into a high-grade lymphoma&#41; responds poorly to treatment and entails a particularly bad prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The pathobiological characteristics and clinical outcome of DLBCL are heterogeneous with 3 major groups correlated with outcome having been identified according to their cell-of-origin &#40;COO&#41; by gene expression profiling &#40;GEP&#41;&#58; germinal center B-cell-like &#40;GCB&#41;&#44; activated B-cell-like &#40;ABC&#41;&#44; and unclassified&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">16</span></a> Several algorithms have been developed using immunohistochemical markers in an attempt to reproduce the GEP results and establish the COO using more readily available technology&#46; The Hans algorithm is most commonly used and it classifies DLBCL into GCB and non-GCB&#46; With this method&#44; some groups have identified the COO as an independent prognostic factor for survival in DLBCL&#44;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">17&#8211;18</span></a> while others have not&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">19&#44;20</span></a> To our knowledge&#44; in the rituximab era few studies have analyzed both the survival and the prognostic influence of the COO in TL&#44; particularly TL from low-grade lymphomas other than FL&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Therefore&#44; in the present study we compared the clinical and biological features &#40;including the COO&#41; as well as the prognosis of TL and <span class="elsevierStyleItalic">de novo</span> DLBCL treated with immunochemotherapy in a single institution&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0030" class="elsevierStylePara elsevierViewall">The records of 163 consecutive <span class="elsevierStyleItalic">de novo</span> DLBCL and 31 TL diagnosed from 2003 to 2012 in our institution were reviewed&#46; Only patients treated with immunochemotherapy were selected&#46; In all cases&#44; the diagnosis was made by tissue biopsy&#46; Patients with HIV-infection&#44; those from whom a biopsy specimen was unavailable for revision and patients with specific subtypes of DLBCL such as primary cutaneous DLBCL&#44; primary central nervous system lymphoma or primary mediastinal DLBCL&#44; were excluded from the study&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The main clinical and biological data were collected&#44; as were the treatment and outcome of both the prior low-grade and the high-grade lymphoma&#46; The COO was established by means of the Hans algorithm&#44; which uses the imunohistochemical expression of CD10&#44; BCL6 and MUM1 on formalin-fixed-paraffin-embedded tissue sections to classify DLBCL into GCB and non-GCB&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">17</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">TL was defined as biopsy-proven DLBCL in patients with a previous diagnosis of a low-grade lymphoproliferative disorder &#40;FL&#44; CLL&#44; MZL&#41; or as cases with both DLBCL and a low-grade lymphoproliferative disorder diagnosed at the same time &#40;in the same or another lymph node&#41;&#46; This latter situation&#44; known as composite lymphoma&#44; is often considered TL at diagnosis&#44;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">6&#44;20&#44;21</span></a> based on the molecular evidence of a clonal relationship between DLBCL and FL&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">22&#44;23</span></a> The study received institutional approval by the ethical committee of Germans Trias I Pujol Hospital &#40;code LT2015&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Baseline demographic and clinical and biological characteristics are presented as median and range for continuous variables and frequency and percentage for categorical variables&#46; Comparisons of these variables between patient groups were performed by the <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&#44; the Fisher&#39;s exact&#44; Student&#39;s-<span class="elsevierStyleItalic">t</span> or Mann&#8211;Whitney&#39;s <span class="elsevierStyleItalic">U</span> test&#44; as appropriate&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Complete response criteria were according to previously reported&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a> Time to transformation &#40;TTT&#41; was defined as the time interval between the diagnosis of the low-grade lymphoma and the diagnosis of TL&#46; Progression-free survival &#40;PFS&#41; was defined as the time from diagnosis to relapse&#44; progression or death due to any cause&#46; Overall survival &#40;OS&#41; was defined as the time from diagnosis to the time of death by any cause&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The Kaplan&#8211;Meier method was used to calculate the OS and PFS curves&#44; and the log-rank test was used to compare the survival between groups &#40;TL and <span class="elsevierStyleItalic">de novo</span> DLBCL&#41;&#46; The variables that showed a difference between the two groups with a <span class="elsevierStyleItalic">p</span> value &#60;0&#46;2&#44; and were considered clinically relevant&#44; were also included to perform the multivariate analyses using Cox&#39;s proportional hazards regression model&#46; All these studies were performed using SPSS v15&#46;0 software &#40;IBM&#44; Somer&#44; NY&#41;&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Patients</span><p id="par0060" class="elsevierStylePara elsevierViewall">Of 163 patients with <span class="elsevierStyleItalic">de novo</span> DLBCL&#44; 22 were excluded because of HIV-positive status and 29 because the diagnostic tissue sample was not available for revission&#46; Three patients with primary cutaneous DLBCL leg type&#44; 2 with primary mediastinal DLBCL and 6 patients not treated with immunochemotherapy &#40;including 4 primary CNS lymphomas&#41; were also excluded from the study&#46; Of 31 TL&#44; 2 patients were excluded because they were not treated with immunochemotherapy&#46; One-hundred and one <span class="elsevierStyleItalic">de novo</span> DLBCL and 29 TL were finally included in the study&#46; Of the 29 TL&#44; 10 were composite lymphomas &#40;considered as TL at diagnosis&#41;&#44; 9 had a previous diagnosis of FL&#44; 6 of MZL and 4 of CLL&#46; As shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; there were no differences between the two groups&#44; other than CD10-positivity&#46; International prognostic index &#40;IPI&#41;&#44; a score that encompasses the most important clinical and analytical prognostic variables and which defines broadly different prognostic groups&#44; did not differ between TL and <span class="elsevierStyleItalic">de novo</span> DLBCL&#46; 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<span class="elsevierStyleItalic">vs&#46;</span> 30&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#59; consequently&#44; TL was more frequently GCB &#40;16 of 23 &#91;70&#37;&#93;&#41; than <span class="elsevierStyleItalic">de novo</span> DLBCL &#40;32 of 76 &#91;42&#37;&#93;&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;031&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Treatment and outcome of the low-grade lymphoma before transformation</span><p id="par0070" class="elsevierStylePara elsevierViewall">Ten patients with low-grade lymphomas were treated with immunochemotherapy&#44; including 6 FL&#44; 3 MZL and 1 CLL&#46; Five cases received R-CHOP&#44; 3 R-CVP&#44; 1 R-FCM &#40;rituximab&#44; fludarabine&#44; cyclophosphamide and mitoxantrone&#41; and the remaining patient underwent splenectomy followed by rituximab and chlorambucil&#46; None of these patients received maintenance with rituximab&#46; Nine patients &#40;3 FL&#44; 3 MZL&#44; 3 CLL&#41; did not receive rituximab at all&#58; 4 patients who did not receive any treatment before transformation&#44; 2 cases treated only with surgery&#44; and 3 who received chemotherapy without rituximab&#46; Ten were composite lymphomas and hence considered as TL at diagnosis&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Patients who received immunochemotherapy for the low-grade lymphoma &#40;No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41; transformed at a median of 3&#46;6 years &#40;range&#58; 0&#46;6&#8211;6&#46;6&#41; after the initial diagnosis&#44; while those that did not &#40;No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41;&#44; transformed after a median of 2&#46;6 years &#40;range&#58; 0&#46;4&#8211;22&#41;&#46; The 5-year OS probability for these two groups after transformation was 50&#37; &#40;95&#37;CI&#58; 19&#37;-81&#37;&#41; and 60&#37; &#40;95&#37;CI&#58; 24&#37;-96&#37;&#41;&#44; respectively &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;110&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Treatment and outcome of the high-grade lymphoma &#40;TL and <span class="elsevierStyleItalic">de novo</span> DLBCL&#41;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Twenty patients with TL were treated with R-CHOP &#40;rituximab&#44; cyclophosphamide&#44; doxorubicin&#44; vincristine and prednisone&#41;&#46; Other immunochemotherapy regimens used were R-ESHAP &#40;rituximab&#44; etoposide&#44; cisplatin&#44; cytarabine and prednisone &#91;5 cases&#93;&#41;&#44; R-CVP &#40;rituximab&#44; cyclophosphamide&#44; vincristine and prednisone &#91;3 cases&#93;&#41; and R-GEMOX &#40;rituximab&#44; gemcitabine&#44; cisplatin &#91;1 case&#93;&#41;&#46; Four patients received radiotherapy &#40;RDT&#41; as part of the first line treatment&#46; Five TL cases received consolidation with high-dose chemotherapy and ASCT &#40;4 after R-CHOP&#41; and 2 with allogeneic stem cell transplantation after achieving the first complete response &#40;CR&#41;&#46; Ninety-one patients with <span class="elsevierStyleItalic">de novo</span> DLBCL were treated with R-CHOP&#46; Other regimens used were R-CVP &#40;6 cases&#41; and EPOCH-R &#40;etoposide&#44; prednisone&#44; vincristine&#44; cyclophosphamide&#44; doxorubicin and rituximab&#41; in 2 cases and dose-intensive chemotherapy including rituximab and high-dose methotrexate and cytarabine<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a> in 2 cases&#46; Twenty-seven patients received RDT&#46; No patient with <span class="elsevierStyleItalic">de novo</span> DLBCL received stem cell transplantation in first CR&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">There were no differences in the CR rate between TL &#40;18 of 29&#41; and <span class="elsevierStyleItalic">de novo</span> DLBCL &#40;66 of 101&#41; after the first line therapy &#40;62&#37; <span class="elsevierStyleItalic">vs</span> 66&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;825&#41;&#46; Furthermore&#44; there were no differences in OS or in PFS &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; with a median follow-up of 4&#46;5 years&#46; Multivariate analyses for OS and PFS of the whole series including TL&#44; Ann-Arbor stages III&#47;IV and bone marrow infiltration as unfavorable factors&#44; showed a lack of prognostic impact on survival in any of them&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">There were no differences between GCB TL and GCB <span class="elsevierStyleItalic">de novo</span> DLBCL or in OS &#40;5yr&#46; OS &#91;95&#37; CI&#93;&#58; 62&#37; &#91;38&#37;-86&#37;&#93; <span class="elsevierStyleItalic">vs&#46;</span> 63&#37; &#91;44&#37;-82&#37;&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;850&#41; or PFS &#40;5 yr&#46; PFS&#58; 42&#37; &#91;17&#37;-67&#37;&#93; <span class="elsevierStyleItalic">vs&#46;</span> 60&#37; &#91;41&#37;-79&#37;&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;204&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Patients treated with R-CHOP without transplantation in CR &#40;14 patients in the TL group and 76 in the <span class="elsevierStyleItalic">de novo</span> DLBCL group&#41; were analyzed separately&#46; Again&#44; there were no differences in 5-year OS or PFS probabilities between TL and <span class="elsevierStyleItalic">de novo</span> DLBCL &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; even though the groups were no longer similar in terms of stage at diagnosis &#40;the TL group had a higher percentage of cases presenting in advanced stages &#91;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#93;&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">In the multivariate analyses restricted to patients who received R-CHOP&#44; without SCT consolidation&#44; advanced stage was an adverse prognostic factor for OS &#40;and a trend for PFS&#41; while TL was not an unfavorable factor for either OS or for PFS &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Only one out of the 7 patients who received SCT &#40;5 ASCT and 2 allogeneic&#41; as first line treatment &#40;all in the TL group&#41; had an advanced stage at diagnosis of TL&#44; while 5 presented with localized disease and the information was not available in the remaining patient&#46; All 5 patients treated with ASCT were alive at the time of data collection&#59; 4 were in CR while the remaining patient was in partial response&#46; The 2 patients who received allogeneic stem cell transplantation&#44; in spite of CR died of infectious complications&#44; 1 and 4 years after transplantation&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">At the time of data collection&#44; 13 patients with TL had died&#59; 10 due to lymphoma progression and 3 due to infection&#44; including the two patients who received allogeneic stem cell transplantation&#46; In the <span class="elsevierStyleItalic">de novo</span> DLBCL group&#44; 33 patients had died&#44; 20 due to lymphoma progression&#44; 8 due to infection&#44; and 5 due to other multiple causes unrelated to the disease or the treatment&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">In the present study&#44; patients with TL treated with immunochemotherapy seemed to have a similar CR rate and 5-year OS and PFS probability as those with <span class="elsevierStyleItalic">de novo</span> DLBCL&#46; Despite the limitations of the study&#44; these findings reflect an improvement in the prognosis of TL treated with immunochemotherapy compared to the pre-rituximab era&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">1&#44;2</span></a> The demographic and clinical characteristics were similar in both groups&#46; Regarding the biological features of the tumor&#44; the data show that the COO of TL is dependent on the low-grade lymphoma from which it evolves&#46; TL from MZL and CLL were non-GCB in all cases&#44; while all TL from FL were GCB&#46; In our series&#44; TL were more frequently GCB because it most often transformed from FL or was diagnosed synchronously with this lymphoma&#44; as shown in other series&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">9&#44;20&#44;26</span></a> To our knowledge&#44; this issue has not been analyzed for TL derived from lymphoproliferative neoplasms other than FL&#44; and our data show that the COO was non-GCB in these cases&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The similar outcomes of patients with TL and <span class="elsevierStyleItalic">de novo</span> DLBCL found in our series are in agreement the results of other authors&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">3&#8211;5&#44;8&#44;9</span></a> Since the introduction of rituximab for the treatment of CD20-positive lymphomas&#44; the prognosis of TL has improved&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">1&#44;2</span></a> A recent large prospective study including patients with FL showed a 5-year OS probability of 75&#37; after transformation&#44; a notable improvement over those obtained before immunochemotherapy27&#46; This study also showed a slightly worse prognosis in patients with DLBCL diagnosed after the diagnosis of FL compared to those diagnosed simultaneously&#44; a result that we could not examine in our series due to the small size of the groups&#46; Concerning the GCB subgroup&#44; there were no differences in the prognosis between TL and <span class="elsevierStyleItalic">de novo</span> DLBCL&#46; Unfortunately&#44; the small sample size of the non-GCB TL did not allow to compare the outcomes of these patients and those of the non-GCB <span class="elsevierStyleItalic">de novo</span> DLBCL patients&#46; As the non-GCB origin is known to carry a worse prognosis&#44; at least in <span class="elsevierStyleItalic">de novo</span> DLBCL&#44; larger series are needed in order to establish whether the prognosis of non-GCB TL is also similar to that of non-GCB <span class="elsevierStyleItalic">de novo</span> DLBCL treated with immunochemotherapy&#46; Furthermore&#44; we found a similar OS and PFS in TL and <span class="elsevierStyleItalic">de novo</span> DLBCL taking into account only patients treated with R-CHOP without SCT&#46; A large&#44; recently published series&#44; including <span class="elsevierStyleItalic">de novo</span> DLBCL and TL treated with R-CHOP showed the same conclusion&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a> Interestingly&#44; despite having similar outcomes&#44; TL patients from our series were more likely to present in advanced stage&#44; which on multivariate analysis was the only adverse risk factor found&#44; in accordance with previous studies in patients with TL&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">2&#44;28</span></a> These data&#44; together with those from other series&#44;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">4&#44;5&#44;29</span></a> suggest that consolidation with ASCT after R-CHOP is not needed in patients with TL&#46; Several studies have shown a favorable effect of consolidation with ASCT for the treatment of TL&#46; However&#44; these studies were biased in that patients not undergoing ASCT most often had chemo-resistant or progressive disease&#44; had comorbidities&#44; worse performance status or were unable to mobilize enough stem cells for the procedure&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">4&#44;30</span></a> In our study only 1 patient receiving ASCT presented with advanced stage at diagnosis of TL&#44; which confirms that patients with better baseline conditions and&#47;or a less aggressive disease undergo ASCT&#46; This selection bias makes difficult to assess the real benefits that ASCT may have in this population&#46; On the other hand&#44; no study to date has shown that patients do not benefit from ASCT&#46; Other post-induction strategies&#44; such as rituximab maintenance or consolidation with radioimmunotherapy&#44; could also be considered in certain patients&#44; as these patients may still have a low-grade component&#46; In fact&#44; a recent retrospective series found consolidation with radioimmunotherapy to be an efficacious strategy in patients with TL that were not eligible for ASCT&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">31</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The most frequent cause of death of patients with TL was lymphoma progression&#46; On the other hand&#44; the two patients who received allogeneic stem cell transplantation ultimately died of sepsis while in CR&#46; Despite the small sample size&#44; similar results have been described in the literature&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">32</span></a> indicating that allogeneic SCT is very effective for the control of the disease but carries a very high rate of transplant-related mortality&#44; mainly associated with the immunosuppression and graft-<span class="elsevierStyleItalic">versus</span>-host disease&#46; On the other hand&#44; the outcomes after allogeneic SCT are very variable<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">33</span></a> &#40;3-year PFS and OS probabilities of up to 83&#37; and 85&#37;&#44; respectively&#44; have been described<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">34</span></a>&#41;&#44; depending on both the institution and the patient selection and therefore&#44; it might be an appropriate option for some patients&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">With regard to the treatment of indolent lymphoma&#44; the addition of rituximab seems to influence the TTT&#46; In our study&#44; the TTT in patients receiving immunochemotherapy for indolent lymphoma was 3&#46;6 years&#44; being 2&#46;6 years in those treated without rituximab&#46; Some studies have found a shorter TTT as well as a more aggressive course of high-grade lymphomas in patients receiving rituximab as part of the treatment for the indolent lymphoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">3&#44;30</span></a> In a large prospective series&#44; treatment of FL with immunochemotherapy was correlated with delayed progression to TL<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">8</span></a> and in another one&#44; rituximab maintenance of patients with FL was correlated with a decreased risk of TL&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a> In our study&#44; no differences were observed in prognosis after transformation between patients who received rituximab for the indolent lymphoma and those who did not&#46; This lack of differences may be due to the small sample size&#44; since other series analyzing the effect of immunochemotherapy for low-grade lymphoma on the prognosis of TL have described a better prognosis for rituximab-naive patients after transformation&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">3&#44;30</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">One of the limitations of this study is its retrospective nature&#44; which led to pooling heterogeneously-treated patients &#40;importantly&#44; patients treated and not treated with regimens including anthracyclines and patients receiving and not receiving SCT&#41;&#46; The limited number of cases did prevent certain analyses to be performed&#44; particularly the potential benefits of undergoing SCT&#46; Similarly&#44; the outcomes of TL from FL could not be compared with those of TL from the CLL and MZL subgroups&#44; which would have been interesting for comparing GCB <span class="elsevierStyleItalic">vs&#46;</span> non-GCB TL&#46; Furthermore&#44; chromosomal rearrangement of the <span class="elsevierStyleItalic">MYC</span> and <span class="elsevierStyleItalic">BCL2</span> genes&#44; which are known to impact prognosis in <span class="elsevierStyleItalic">de novo</span> DLBCL&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a> was not examined in the majority of patients&#46; This would be an essential biological analysis in any prospective study concerning the prognosis of TL&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In summary&#44; in this series&#44; although retrospective and heterogeneous&#44; the prognosis of patients with TL and <span class="elsevierStyleItalic">de novo</span> DLBCL treated with immunochemotherapy seems to be similar&#44; especially in those receiving R-CHOP without SCT&#44; in accordance with other reports performed in the rituximab era&#46; The treatment of indolent lymphoma with regimens including rituximab may delay transformation but it does not seem influence on survival&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The TL phenotype was GCB on transformation from FL and non-GCB on transformation from MZL and CLL&#46; Further studies including a larger number of patients are needed to determine whether the prognosis of TL from FL is different from that of TL from other indolent lymphomas treated with immunochemotherapy&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Funding</span><p id="par0150" class="elsevierStylePara elsevierViewall">This work was funded in part by a grant from the Instituto de Salud Carlos III&#44; Ministerio de Economia y Competividad&#44; Spain&#44; Red Tem&#225;tica de Investigaci&#243;n Cooperativa en C&#225;ncer &#40;RTICC&#44; FEDER&#41; &#40;RD12&#47;0036&#47;0044&#41;&#59; 2014 SGR225 &#40;GRE&#41; Generalitat de Catalunya&#59; economical support from Fundaci&#243; Internacional Josep Carreras&#46; The research leading to this article has received funding from &#8220;la Caixa Foundation&#8221;&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interest</span><p id="par0155" class="elsevierStylePara elsevierViewall">MJB and JTN received a research grant from CELGENE Spain&#46;</p></span></span>"
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              "titulo" => "Cell of origin"
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              "titulo" => "Treatment and outcome of the low-grade lymphoma before transformation"
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              "titulo" => "Treatment and outcome of the high-grade lymphoma &#40;TL and de novo DLBCL&#41;"
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    "fechaRecibido" => "2016-03-27"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The prognosis of diffuse large B-cell lymphomas &#40;DLBCL&#41; transformed from indolent lymphoma &#40;TL&#41; has been considered poorer than that of <span class="elsevierStyleItalic">de novo</span> DLBCL&#46; However&#44; it seems to have improved since the introduction of rituximab&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We compared the characteristics &#40;including the cell-of-origin&#41;&#44; and the prognosis of 29 patients with TL and 101 with <span class="elsevierStyleItalic">de novo</span> DLBCL treated with immunochemotherapy&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Patients with TL and <span class="elsevierStyleItalic">de novo</span> DLBCL had similar characteristics&#46; All TL cases evolving from follicular lymphoma were germinal-center B-cell-like&#44; while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like&#46; The complete response rate was similar in TL and <span class="elsevierStyleItalic">de novo</span> DLBCL &#40;62 <span class="elsevierStyleItalic">vs&#46;</span> 66&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">0</span>&#46;825&#41;&#46; The 5-year overall and progression-free survival probabilities &#40;95&#37; CI&#41; were 59&#37; &#40;40&#8211;78&#41; and 41&#37; &#40;22&#8211;60&#41; for TL and 63&#37; &#40;53&#8211;73&#41; and 60&#37; &#40;50&#8211;70&#41; for <span class="elsevierStyleItalic">de novo</span> DLBCL&#44; respectively &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">0</span>&#46;732 for overall survival and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">0</span>&#46;169 for progression-free survival&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In this study&#44; the prognosis of TL and <span class="elsevierStyleItalic">de novo</span> DLBCL treated with immunochemotherapy was similar&#46; The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El pron&#243;stico de los linfomas difusos de c&#233;lulas B grandes &#40;LDCBG&#41; transformados de linfomas indolentes &#40;LT&#41; ha sido considerado m&#225;s desfavorable que el pron&#243;stico de LDCBG <span class="elsevierStyleItalic">de novo</span>&#46; Sin embargo&#44; este parece haber mejorado desde la introducci&#243;n de rituximab&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se compararon las caracter&#237;sticas &#40;incluyendo la c&#233;lula de origen&#41; y el pron&#243;stico de 29 pacientes con LT y 101 con LDCBG <span class="elsevierStyleItalic">de novo</span> tratados con inmunoquimioterapia&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con LT y LDCBG <span class="elsevierStyleItalic">de novo</span> ten&#237;an caracter&#237;sticas similares&#46; Todos los casos de LT que evolucionaron de un linfoma folicular fueron linfomas de c&#233;lulas B de tipo centro germinal&#44; mientras que aquellos LT que evolucionaron de un linfoma de la zona marginal o leucemia linfoc&#237;tica cr&#243;nica fueron de tipo no centro germinal&#46; El &#237;ndice de respuesta completa fue similar en los LT y en los LDCBG <span class="elsevierStyleItalic">de novo</span> &#40;62 frente a 66&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;825&#41;&#46; Las probabilidades de supervivencia global y libre de progresi&#243;n a 5 a&#241;os &#40;IC 95&#37;&#41; fueron del 59&#37; &#40;40&#8211;78&#41; y el 41&#37; &#40;22&#8211;60&#41; para LT y del 63&#37; &#40;53&#8211;73&#41; y el 60&#37; &#40;50&#8211;70&#41; para LDCBG <span class="elsevierStyleItalic">de novo</span>&#44; respectivamente &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;732 para supervivencia global y p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;169 para supervivencia libre de progresi&#243;n&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">En este estudio&#44; el pron&#243;stico de los LT y LDCBG <span class="elsevierStyleItalic">de novo</span> tratados con inmunoquimioterapia fue similar&#46; El papel de la intensificaci&#243;n con trasplante de precursores hematopoy&#233;ticos en el tratamiento del LT puede ser cuestionable en la era del rituximab&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Antecedentes"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Pacientes y m&#233;todos"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
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    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Sorigue M&#44; Garcia O&#44; Baptista MJ&#44; Sancho J-M&#44; Tapia G&#44; Mate JL&#44; et al&#46; Pron&#243;stico similar de los linfomas transformados y los linfomas difusos de c&#233;lulas B grandes <span class="elsevierStyleItalic">de novo</span> en pacientes tratados con inmunoquimioterapia&#46; Med Clin &#40;Barc&#41;&#46; 2017&#59;148&#58;243&#8211;249&#46;</p>"
      ]
    ]
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        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Overall survival of the patients with TL compared with <span class="elsevierStyleItalic">de novo</span> DLBCL&#46; &#40;B&#41; Progression free survival of the patients with TL compared with <span class="elsevierStyleItalic">de novo</span> DLBCL&#46;</p>"
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Overall survival of the patients treated with R-CHOP&#58; comparison of TL with <span class="elsevierStyleItalic">de novo</span> DLBCL&#46; &#40;B&#41; Progression free survival of the patients treated with R-CHOP&#58; comparison of TL with <span class="elsevierStyleItalic">de novo</span> DLBCL&#46;</p>"
        ]
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      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
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            "identificador" => "at1"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">TL&#58; transformed lymphoma&#59; DLBCL&#58; Diffuse large B-cell lymphoma&#59; LDH&#58; lactate dehydrogenase&#59; IPI&#58; international prognostic index&#59; GCB&#59; germinal center B-cell&#59; COO&#58; cell-of-origin&#46;</p><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">The results in bold indicate a <span class="elsevierStyleItalic">p</span> with statistical significance&#46;</p>"
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                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">&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">TL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#41;&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">DLBCL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>101&#41;&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"><span class="elsevierStyleItalic">p</span>&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">Total &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41;&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"><span class="elsevierStyleItalic">Male&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#47;29 &#40;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&#47;101 &#40;51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66&#47;130 &#40;51&#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="elsevierStyleItalic">Age&#44; median &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60 &#40;43&#44; 83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64 &#40;24&#44; 87&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;487&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62 &#40;24&#44; 87&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" 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="5" align="left" valign="top"><span class="elsevierStyleItalic">Stage&#44; n &#40;&#37;&#41;</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>I&#8211;II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#47;28 &#40;32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&#47;100 &#40;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;198&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56&#47;128 &#40;44&#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>III&#8211;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#47;28 &#40;68&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&#47;100 &#40;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&#47;128 &#40;56&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></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="elsevierStyleItalic">B symptoms&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#47;26 &#40;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#47;101 &#40;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;651&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&#47;127 &#40;35&#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="elsevierStyleItalic">Bone marrow infiltration&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#47;28 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#47;101 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;182&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#47;129 &#40;19&#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="elsevierStyleItalic">Extranodal disease&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#47;28 &#40;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#47;101 &#40;36&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;379&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&#47;129 &#40;38&#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="elsevierStyleItalic">&#8805;2 extranodal areas&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;28 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#47;101 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;562&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&#47;129 &#40;16&#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="elsevierStyleItalic">High serum LDH&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#47;25 &#40;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&#47;94 &#40;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;507&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#47;119 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" 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="5" align="left" valign="top"><span class="elsevierStyleItalic">IPI&#44; n &#40;&#37;&#41;</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>Low &#40;0&#8211;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#47;25 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&#47;93 &#40;36&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;707&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#47;118 &#40;34&#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>Low&#47;Int &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#47;25 &#40;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#47;93 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#47;118 &#40;31&#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>High&#47;Int &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#47;25 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#47;93 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&#47;118 &#40;20&#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>High &#40;4&#8211;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;25 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#47;93 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&#47;118 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></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="elsevierStyleItalic">CD10-positive&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#47;24 &#40;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#47;89 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">0&#46;002</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&#47;113 &#40;38&#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="elsevierStyleItalic">BCL6-positive&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&#47;23 &#40;87&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">75&#47;94 &#40;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;559&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&#47;117 &#40;81&#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="elsevierStyleItalic">MUM1-positive&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#47;12 &#40;83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&#47;66 &#40;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;772&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#47;78 &#40;77&#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="elsevierStyleItalic">GCB COO&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#47;23 &#40;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&#47;76 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">0&#46;031</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&#47;99 &#40;48&#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="elsevierStyleItalic">Median follow-up&#44; years &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;1 &#40;0&#46;8&#44; 10&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;1 &#40;0&#46;1&#44; 10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;5 &#40;0&#46;1&#44; 10&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of the patients with TL and <span class="elsevierStyleItalic">de novo</span> DLBCL&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">LDH&#58; lactate dehydrogenase&#59; IPI&#58; international prognostic index&#59; GCB&#58; germinal center B-cell&#59; COO&#58; cell-of-origin&#59; FL&#58; Follicular lymphoma&#59; CL&#58; composite lymphoma&#59; MZL&#58; marginal zone lymphoma&#59; CLL&#58; chronic lymphocytic leukemia&#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=""><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">FL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41;&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">MZL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;&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">CLL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&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"><span class="elsevierStyleItalic">Male&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#47;19 &#40;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;6 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;4 &#40;50&#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="elsevierStyleItalic">Age&#44; median &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60 &#40;43&#44; 83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64 &#40;47&#44; 71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57 &#40;51&#44; 64&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" 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="4" align="left" valign="top"><span class="elsevierStyleItalic">Stage&#44; n &#40;&#37;&#41;</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>I&#8211;II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#47;18 &#40;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;6 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;4&#40;75&#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>III&#8211;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#47;18 &#40;78&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#47;6 &#40;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#47;4 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></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="elsevierStyleItalic">B symptoms&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#47;17 &#40;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#47;6 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;3 &#40;67&#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="elsevierStyleItalic">Bone marrow infiltration&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#47;18 &#40;39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#47;6 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#47;4 &#40;0&#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="elsevierStyleItalic">Extranodal disease&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#47;18 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;6 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;4 &#40;50&#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="elsevierStyleItalic">&#8805;2 extranodal areas&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;18 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#47;6 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#47;4 &#40;0&#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="elsevierStyleItalic">High serum LDH&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#47;16 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#47;6 &#40;83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#47;4 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" 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="4" align="left" valign="top"><span class="elsevierStyleItalic">IPI&#44; n &#40;&#37;&#41;</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>Low &#40;0&#8211;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#47;16 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#47;6 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;3 &#40;67&#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>Low&#47;Int &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#47;16 &#40;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;6 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#47;3 &#40;33&#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>High&#47;Int &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;16 &#40;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;6 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#47;3 &#40;0&#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>High &#40;4&#8211;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;16 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#47;6 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#47;3 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></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="elsevierStyleItalic">CD10-positive&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#47;16 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#47;5 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#47;3 &#40;0&#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="elsevierStyleItalic">BCL6-positive&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#47;16 &#40;94&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;4 &#40;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;3 &#40;67&#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="elsevierStyleItalic">MUM1-positive&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#47;6 &#40;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#47;4 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;2 &#40;100&#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="elsevierStyleItalic">GCB COO&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#47;16 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#47;4 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#47;3 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of TL patients according to the type of low grade lymphoma&#46;</p>"
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      4 => array:8 [
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        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">TL&#58; transformed lymphoma&#59; DLBCL&#58; Diffuse large B-cell lymphoma&#59; SCT&#58; stem cell transplantation&#59; LDH&#58; lactate dehydrogenase&#59; IPI&#58; international prognostic index&#59; COO&#58; cell-of-origin&#46;</p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">The results in bold indicate a <span class="elsevierStyleItalic">p</span> with statistical significance&#46;</p>"
          "tablatextoimagen" => array:1 [
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              "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">&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">TL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41;&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">DLBCL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>76&#41;&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"><span class="elsevierStyleItalic">p</span>&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"><span class="elsevierStyleItalic">Male&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#47;14 &#40;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#47;76 &#40;49&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;776&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">Age&#44; median &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60 &#40;43&#44; 72&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61 &#40;24&#44; 83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;840&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" 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="4" align="left" valign="top"><span class="elsevierStyleItalic">Stage&#44; n &#40;&#37;&#41;</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>I&#8211;II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;14 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#47;75 &#40;48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">0&#46;036</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>III&#8211;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#47;14 &#40;86&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&#47;75 &#40;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></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="elsevierStyleItalic">B symptoms&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;13 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&#47;76 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;363&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">Bone marrow infiltration&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#47;14 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#47;76 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;264&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">Extranodal disease&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#47;14 &#40;36&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#47;76 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">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="elsevierStyleItalic">&#8805;2 extranodals areas&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;14 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#47;76 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">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="elsevierStyleItalic">High serum LDH&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#47;12 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#47;69 &#40;51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;756&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" 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="4" align="left" valign="top"><span class="elsevierStyleItalic">IPI&#44; n &#40;&#37;&#41;</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>Low &#40;0&#8211;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#47;12 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#47;68 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>Low&#47;Int &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#47;12 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&#47;68 &#40;34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>High&#47;Int &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#47;12 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#47;68 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>High &#40;4&#8211;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#47;12 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#47;68 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></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="elsevierStyleItalic">CD10-positive&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#47;12 &#40;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&#47;65 &#40;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">0&#46;007</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">BCL6-positive&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#47;12 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#47;69 &#40;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;114&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">MUM1-positive&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#47;4 &#40;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&#47;49 &#40;69&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&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">COO&#58; GCB&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#47;12 &#40;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#47;56 &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of the patients with TL and <span class="elsevierStyleItalic">de novo</span> DLBCL treated with R-CHOP without SCT consolidation&#46;</p>"
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          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">TL&#58; transformed lymphoma&#59; OS&#58; Five-year overall survival&#59; PFS&#58; Five-year progression-free survival&#46;</p><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">The results in bold indicate a <span class="elsevierStyleItalic">p</span> with statistical significance&#46;</p>"
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Unfavorable group&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HR &#40;CI 95&#37;&#41;&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"><span class="elsevierStyleItalic">p</span>&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">TL <span class="elsevierStyleItalic">vs&#46; de novo</span> DLBCL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;7 &#40;0&#46;3&#44; 2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;2 &#40;0&#46;5&#44; 2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;633&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">Ann Arbor stage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">III&#8211;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;5 &#40;1&#46;1&#44; 5&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">0&#46;035</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;9 &#40;0&#46;9&#44; 4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;098&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Multivariate analyses of patients treated with RCHOP &#40;without SCT consolidation&#41;&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:35 [
            0 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Montoto"
                            1 => "A&#46;J&#46; Davies"
                            2 => "J&#46; Matthews"
                            3 => "M&#46; Calaminici"
                            4 => "A&#46;J&#46; Norton"
                            5 => "J&#46; Amess"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2006.09.3260"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2007"
                        "volumen" => "25"
                        "paginaInicial" => "2426"
                        "paginaFinal" => "2433"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17485708"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0022534710035068"
                          "estado" => "S300"
                          "issn" => "00225347"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Population-based analysis of incidence and outcome of transformed non-Hodgkin&#39;s lymphoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;J&#46; Al-Tourah"
                            1 => "K&#46;K&#46; Gill"
                            2 => "M&#46; Chhanabhai"
                            3 => "P&#46;J&#46; Hoskins"
                            4 => "R&#46;J&#46; Klasa"
                            5 => "K&#46;J&#46; Savage"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2008.16.0283"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2008"
                        "volumen" => "26"
                        "paginaInicial" => "5165"
                        "paginaFinal" => "5169"
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