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"documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2024;162:83-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Primary adrenal carcinoma: Experience of 8 cases" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "83" "paginaFinal" => "85" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Carcinoma primario de corteza suprarrenal: experiencia de 8 casos" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "María José Vallejo Herrera, Stella González Romero, Verónica Vallejo Herrera" "autores" => array:3 [ 0 => array:2 [ "nombre" => "María José" "apellidos" => "Vallejo Herrera" ] 1 => array:2 [ "nombre" => "Stella" "apellidos" => "González Romero" ] 2 => array:2 [ "nombre" => "Verónica" "apellidos" => "Vallejo Herrera" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775323005481" "doi" => "10.1016/j.medcli.2023.09.002" "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/S0025775323005481?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020623005508?idApp=UINPBA00004N" "url" => "/23870206/0000016200000002/v2_202401240540/S2387020623005508/v2_202401240540/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S238702062300551X" "issn" => "23870206" "doi" => "10.1016/j.medcle.2023.12.003" "estado" => "S300" "fechaPublicacion" => "2024-01-26" "aid" => "6422" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2024;162:73-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>" "titulo" => "Factor XI inhibitors: A new era in antithrombotic therapy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "73" "paginaFinal" => "76" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Inhibidores del factor XI: una nueva era en el tratamiento antitrombótico" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1395 "Ancho" => 2567 "Tamanyo" => 162876 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Role of factor XI in haemostasis and thrombosis.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">PolyP, polyphosphate; NET, neutrophil extracellular trap.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José A. Páramo, Maria Marcos-Jubilar" "autores" => array:2 [ 0 => array:2 [ "nombre" => "José A." "apellidos" => "Páramo" ] 1 => array:2 [ "nombre" => "Maria" "apellidos" => "Marcos-Jubilar" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775323005511" "doi" => "10.1016/j.medcli.2023.09.003" "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/S0025775323005511?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702062300551X?idApp=UINPBA00004N" "url" => "/23870206/0000016200000002/v2_202401240540/S238702062300551X/v2_202401240540/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Diagnosis and treatment</span>" "titulo" => "Myelodysplastic neoplasms" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "77" "paginaFinal" => "82" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "María Panizo Inogés, Ana Alfonso-Pierola" "autores" => array:2 [ 0 => array:2 [ "nombre" => "María" "apellidos" => "Panizo Inogés" ] 1 => array:4 [ "nombre" => "Ana" "apellidos" => "Alfonso-Pierola" "email" => array:1 [ 0 => "aalfonso@unav.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Departamento de Hematología y Hemoterapia, Clínica Universidad de Navarra, Pamplona, Navarra, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neoplasias mielodisplásicas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1574 "Ancho" => 2931 "Tamanyo" => 320945 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Treatment algorithm for myelodysplastic neoplasms. EPO: erythropoietin; HMA: hypomethylating agents.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Myelodysplastic neoplasms (World Health Organization [WHO] 2022) or myelodysplastic syndromes (International Consensus Classification [ICC] 2022), in both classifications abbreviated as MDS, are a heterogeneous group of clonal diseases of pluripotent haematopoietic stem cells that occur as a consequence of the progressive acquisition of somatic mutations.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> They have a higher incidence in males, especially after the age of 70. They are characterised by ineffective haematopoiesis in the form of cytopenia and the presence of ≥ 10% dysplasia in one or more cell lines of the myeloid line. Its main risk is progression to acute myeloblastic leukaemia (AML).<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The characteristic heterogeneity of this disease means that patients have a diversity of prognoses, with survivals ranging from less than one year to more than 10 years. All these challenges underline the need to constantly review the diagnostic, classification and prognostic criteria for these patients in order to individualise therapeutic strategies.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Diagnosis</span><p id="par0015" class="elsevierStylePara elsevierViewall">The diagnosis of MDS, considering the WHO 2022 criteria, requires the presence of cytopenia and dysplasia in the myeloid series or the presence of 5−19% blasts in bone marrow.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A required criterion is the occurrence of cytopenia defined as: haemoglobin < 130 g/l in males and < 120 g/l in females for anaemia, neutrophils < 1,8 × 10<span class="elsevierStyleSup">9</span>/l for neutropenia and platelets < 150 × 10<span class="elsevierStyleSup">9</span>/l for thrombocytopenia.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A bone marrow aspirate, which is usually hypercellular despite peripheral cytopenia, is essential for the study of dysplasia and myeloid blasts. We define a series as dysplastic when it has at least 10% of dysplastic elements. On the other hand, it is essential to count myeloid blasts. The presence of 5−19% blasts is diagnostic of MDS, in the absence of some AML-defining genetic alterations (<span class="elsevierStyleItalic">KMT2A</span>, <span class="elsevierStyleItalic">MECOM</span> or <span class="elsevierStyleItalic">NUP98</span> rearrangements or the presence of <span class="elsevierStyleItalic">NPM1</span> mutations).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">A bone marrow biopsy at diagnosis is recommended, in addition to bone marrow aspirate, to identify hypoplastic MDS and those with fibrosis.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The role of flow cytometry is limited, as there are no immunophenotypic alterations characteristic of MDS by themselves, but scores (OGATA) have been developed to help in the differential diagnosis.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Finally, cytogenetic study by conventional karyotyping is indispensable at the time of diagnosis, as it is key for the prognostic estimation of MDS patients and confirms clonality, which can be very useful in patients with very subtle dysplastic changes.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Molecular study is becoming increasingly important in the diagnosis of MDS as somatic variants have been identified in a high percentage of patients <span class="elsevierStyleItalic">(</span>80-90%), predominantly in splicing, transcription regulation, DNA methylation or transduction genes. The main genes affected include <span class="elsevierStyleItalic">SF3B1</span>, <span class="elsevierStyleItalic">TET2</span>, <span class="elsevierStyleItalic">SRSF2</span>, <span class="elsevierStyleItalic">DNMT3A</span> and <span class="elsevierStyleItalic">RUNX1</span>. It is important to note that these alterations are not exclusive to MDS and can occur in other entities. In addition, the <span class="elsevierStyleItalic">SF3B1</span> and <span class="elsevierStyleItalic">TP53</span> gene variants have acquired a fundamental role, as they are necessary for the correct classification of MDS.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In recent years, several entities have emerged that do not meet the criteria for MDS but share some of its characteristics and are part of the differential diagnosis of MDS: clonal haematopoiesis of indeterminate potential (CHIP), idiopathic cytopenia of undetermined significance (ICUS) and clonal cytopenia of undetermined significance (CCUS).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Classification</span><p id="par0055" class="elsevierStylePara elsevierViewall">Today, we find ourselves in a period of transition with 2 classifications in place. Although these classifications share many similarities, they also exhibit minor differences beyond the scope of this review.</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">World Health Organization classification 2022</span><p id="par0060" class="elsevierStylePara elsevierViewall">The new World Health Organisation (WHO 2022) classification establishes 2 major groups of MDS (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>); MDS defined by genetic abnormalities (<span class="elsevierStyleItalic">SF3B1</span>, 5q and <span class="elsevierStyleItalic">TP53</span>) and those defined by morphological abnormalities. MDS with mutated <span class="elsevierStyleItalic">SF3B1</span> is established as a separate entity because <span class="elsevierStyleItalic">SF3B1</span> is present in approximately 90% of patients with > 5% ring sideroblasts.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">From a morphological point of view, they are classified into 2 groups, MDS with low blast count and MDS with increased blasts. It also introduces a new category of hypoplastic myelodysplastic syndromes and MDS with fibrosis.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">International Consensus Classification 2022</span><p id="par0070" class="elsevierStylePara elsevierViewall">The International Consensus Classification (ICC 2022) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>) also establishes separate subgroups based on <span class="elsevierStyleItalic">SF3B1</span>, 5q and <span class="elsevierStyleItalic">TP53</span>. In addition, one of the major variations of this classification is the creation of the MDS/AML subgroup that includes patients with 10−19% blasts in the absence of AML-defining genetic alterations.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">One of the major novelties in both classifications is <span class="elsevierStyleItalic">TP53</span>-mutated MDS. It has recently been shown that patients with a single <span class="elsevierStyleItalic">TP53</span> mutation have an overall survival (OS) and progression-free survival (PFS) similar to <span class="elsevierStyleItalic">wild-type</span> patients. However, patients with <span class="elsevierStyleItalic">multi-hit TP53</span> have a poor prognosis in terms of overall survival and transformation to AML.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The WHO 2022 update has reclassified these patients into a subgroup called MDS with biallelic <span class="elsevierStyleItalic">TP53</span> inactivation within MDS with defining genetic alterations. On the other hand, the ICC has separated these patients into a distinct entity called <span class="elsevierStyleItalic">TP53</span>-mutated myeloid neoplasms, which includes: <span class="elsevierStyleItalic">TP53</span>-mutated MDS, <span class="elsevierStyleItalic">TP53</span>-mutated MDS/AML and <span class="elsevierStyleItalic">TP53</span>-mutated AML.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Prognosis</span><p id="par0080" class="elsevierStylePara elsevierViewall">The prognosis of MDS is highly variable, and an accurate estimation of prognosis is essential as it impacts on treatment decisions.</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Revised International Prognostic Scoring System</span><p id="par0085" class="elsevierStylePara elsevierViewall">To date, the main tool to stratify the prognosis of these patients was the <span class="elsevierStyleItalic">Revised International Prognostic Scoring System</span> (IPSS-R). This model classified patients into 5 prognostic subgroups based on age, cytopenia, percentage of blasts in bone marrow and cytogenetics, but did not include somatic mutations<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). The Spanish Myelodysplastic Syndromes group reclassified these 5 risk categories into 2 groups: low-risk MDS, which includes those with very low, low IPSS-R and some intermediate subgroups with a survival of less than 30 months; and high-risk MDS, which includes high- and very high-risk patients and some intermediate-risk subgroups (score ≥ 3.5 and any of the following: high or very high risk cytogenetics; platelets < 30 × 10<span class="elsevierStyleSup">9</span>/l; neutrophils < 0.5 × 10<span class="elsevierStyleSup">9</span>/l; WHO grade 2–3 myelofibrosis; TP53 somatic mutation) with survivals greater than 30 months.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">International Prognostic Scoring System Molecular</span><p id="par0090" class="elsevierStylePara elsevierViewall">In recent years, multiple molecular alterations with an impact on MDS have become known. These data have been incorporated into a new prognostic system, the <span class="elsevierStyleItalic">International Prognostic Scoring System Molecular</span> (IPSS-M), which stratifies patients into 6 risk categories based on cytopenias, cytogenetics and somatic mutations of 31 genes<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>. The 5 most common are <span class="elsevierStyleItalic">U2AF1</span>, <span class="elsevierStyleItalic">ASXL1</span>, <span class="elsevierStyleItalic">RUNX1</span>, <span class="elsevierStyleItalic">SF3B1</span> and <span class="elsevierStyleItalic">TP53</span><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Using this new prognostic tool, the study by Junying Wu et al. reclassified 41% of patients from the IPSS-R; 70% of them were reclassified to a worse prognosis while 30% were included in a better prognostic subgroup.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> This new tool plays an important role, especially in patients over 60 years of age.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Treatment</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Low-risk myelodysplastic neoplasms</span><p id="par0100" class="elsevierStylePara elsevierViewall">To date, the goal of treatment in low-risk patients is to improve the patient's quality of life (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The main clinical manifestation in this group of patients is anaemia, so patients often require transfusion support, which is associated with iron overload and poorer survival with a higher likelihood of progression to AML.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In order to prevent transfusion-associated iron overload, iron chelation is recommended in MDS patients requiring periodic transfusion support and a life expectancy of at least one year, and in those candidates for allogeneic transplantation.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Initiation of treatment is not indicated in transfusion-independent patients and close laboratory monitoring should be implemented.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Antibiotic prophylaxis and the use of growth factors in neutropenic patients is not routinely indicated.</p><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Erythropoiesis-stimulating agents</span><p id="par0120" class="elsevierStylePara elsevierViewall">Erythropoiesis-stimulating agents (ESAs) are the first therapeutic option in patients with low-risk MDS and anaemia. Multiple studies support treatment of this MDS subgroup with ESAs, with response rates between 30–60%, for patients with haemoglobin < 10 g/dl or in those with even higher numbers but with associated symptoms. High doses of these agents should be used: 60,000 U weekly of humanised recombinant erythropoietin or 500 μg of darbepoetin alfa every 3 weeks.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In order to identify patients who responded to ESAs treatment, an algorithm was developed to classify patients into three groups (good, intermediate or poor response) according to endogenous erythropoietin levels (<100, 100–500, > 500 U/l) and transfusion requirements (<2 red cell concentrates/month, ≥2 red cell concentrates/month).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Currently, initiation of ESAs is not recommended for patients with two poor response criteria given their low likelihood of response.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Lenalidomide</span><p id="par0130" class="elsevierStylePara elsevierViewall">It is an immunomodulatory and anti-angiogenic agent. In the context of low-risk MDS, early phase II studies showed that treatment with lenalidomide 10 mg/day for 21 days in 28-day cycles achieved a significant reduction in transfusion requirements in 76% of patients, with 67% achieving transfusion independence.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> The benefits were greatest in patients with MDS with 5q deletion (MDS 5q), so the phase 3 trial (MDS-004) focused on this population. MDS-004 compared lenalidomide 10 mg for 21 days or 5 mg for 28 days versus placebo in patients with 5q MDS and transfusion dependence. Patients treated in the lenalidomide arm achieved higher rates of transfusion independence versus placebo, with the lenalidomide arm showing a better response (56.1 and 42.9% versus 5.9%; both p < 0.001). In addition, patients treated with 10 mg achieved higher numbers of cytogenetic responses (50 versus 25% on lenalidomide 5 mg). Overall survival of lenalidomide-treated patients was 56.5%, with a risk of progression to AML of 25.1%.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">These results gave lenalidomide approval as a treatment for patients with low-risk, transfusion-dependent MDS and 5q deletion who either have a low likelihood of responding to EPO or have failed to respond to EPO.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Luspatercept</span><p id="par0140" class="elsevierStylePara elsevierViewall">It is a molecule consisting of the <span class="elsevierStyleItalic">transforming growth factor beta</span> (TGF-beta) receptor and the IgG1 constant fraction, whose mechanism of action is based on inhibition of the TGF-beta pathway.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The phase 2 PACE-MDS trial, which included 58 patients with low-risk MDS, observed how 63% of patients receiving high-dose luspatercept (1–1.75 mg/kg) achieved erythroid response, compared to 22% in the low-dose arm (0.125−0.5 mg/kg). Furthermore, patients who responded to luspatercept were mostly those with ≥ TGF-beta 15% ring sideroblasts or with <span class="elsevierStyleItalic">SF3B1</span> mutation.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The MEDALIST study showed that in patients with low-risk MDS, > 15% ring sideroblasts (or > 5% with SF3B1 mutation) and transfusion-dependent, with no response to ESAs or who had required discontinuation of treatment due to adverse effects, luspatercept was superior to placebo in rates of transfusion independence for 8 or more weeks (38 vs. 13%), with a very good safety profile.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">These results have led to the approval of luspatercept for the treatment of MDS patients with ring sideroblasts and transfusion dependence, who have either lost their response to ESAs or who were not candidates for ESAs due to high endogenous erythropoietin.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Allogeneic transplantation</span><p id="par0160" class="elsevierStylePara elsevierViewall">Currently, the only therapeutic alternative with curative potential for patients with myelodysplastic syndrome is allogeneic transplantation. However, this option tends to be considered mainly in high-risk patients given the morbidity and mortality associated with it.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Traditionally, patients with low-risk MDS were not considered candidates for allogeneic transplantation as data had shown that for patients with low and intermediate-1 IPSS, delaying transplantation increased overall survival.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> However, there is some controversy as, while patients with low IPSS did not seem to benefit from early transplantation, those with intermediate-1 IPSS had better responses than patients with high-risk MDS.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The results of a retrospective study conducted by the GESMD showed that in transplanted low-risk MDS patients, overall survival at 3 years was 67%, with an event-free survival of 64%.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Therefore, allogeneic transplantation may become an alternative in young patients with intermediate-1 IPSS and refractory to other therapies, for whom no clinical trial treatment is available.</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">High-risk myelodysplastic neoplasms</span><p id="par0180" class="elsevierStylePara elsevierViewall">The goal of treatment in this subgroup of patients is to modify the course of the disease, prolonging overall survival and progression-free survival to AML (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Hypomethylating agents</span><p id="par0185" class="elsevierStylePara elsevierViewall">Hypomethylating agents (azacitidine or decitabine) are the treatment of choice in high-risk MDS patients who are not transplant candidates. Their role lies in inhibiting DNA methyltransferase, thereby reactivating transcription of tumour suppressor genes.</p><p id="par0190" class="elsevierStylePara elsevierViewall">Already in 2002, a randomised clinical trial developed by the <span class="elsevierStyleItalic">Cancer and Leukaemia Group B</span> (CALGB) cooperative group compared treatment with azacitidine versus best supportive care, confirming a better complete response rate with azacitidine (60 vs. 5%), but also a better survival free of transformation to leukaemia (21 vs. 13 months) and overall survival. In addition, patients treated with azacitidine had a better quality of life.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">A multicentre clinical trial comparing treatment with azacitidine (75 mg/m<span class="elsevierStyleSup">2</span> for 7 days, in 28-day cycles) to the best conventional treatment (supportive care, low-dose cytarabine or intensive chemotherapy) showed that patients treated with azacitidine had a longer overall survival (24.5 vs. 15 months) compared to the control group.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">More recently, a meta-analysis by Garcia et al. using a sample of high-risk MDS patients treated with azacitidine monotherapy showed a complete response rate of 17% with an overall survival of 18.6 months.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Azacitidine is approved in Spain for the treatment of high-risk MDS patients who are not candidates for allogeneic transplantation.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Acute myeloid leukaemia-type chemotherapy</span><p id="par0210" class="elsevierStylePara elsevierViewall">The clinical course of high-risk MDS patients more closely resembles that of those with AML than that of patients with low-risk MDS. Therefore, for many years, the only therapeutic strategy available for this subgroup of patients consisted of AML-type chemotherapy regimens.</p><p id="par0215" class="elsevierStylePara elsevierViewall">In patients with high-risk MDS, intensive treatment with AML-type chemotherapy can achieve complete response rates ranging from 50 to 60% but involves high morbidity and mortality, especially in older patients. In addition, it has been shown that these complete responses are often short-lived at around 8 months and are associated with an increase in refractory disease, which is observed in approximately 20−25% of patients who relapse.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">A study comparing intensive chemotherapy with decitabine in a similar cohort of patients showed that treatment with intensive chemotherapy had statistically inferior overall survival (22 vs. 12 months; p < 0.001).<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Therefore, intensive chemotherapy is especially recommended for young patients (<65 years) with high-risk MDS who are candidates for intensive treatment, but initially do not have a suitable donor for allogeneic transplantation.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Allogeneic transplantation</span><p id="par0230" class="elsevierStylePara elsevierViewall">High-risk patients who are candidates for allogeneic transplantation should be considered for it as it is currently the only curative strategy in MDS. However, it should not be forgotten that it poses significant risks in terms of morbidity and mortality, so it is important to make a good candidate selection.</p><p id="par0235" class="elsevierStylePara elsevierViewall">There is currently no evidence-based recommendation on the ideal timing for allogeneic transplantation. Several decision models propose transplantation in early-stage disease, with low bone marrow blast counts, in high-risk patients (intermediate-2 and high IPSS) as this strategy offers a higher probability of long-term survival and remission.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">The need for cytoreductive treatment remains a major question mark in MDS-related allogeneic transplantation (hypomethylating agents or AML-type chemotherapy) prior to transplantation or direct transplantation. There are no prospective trials offering evidence, so the use of cytoreduction is widely debated.</p><p id="par0245" class="elsevierStylePara elsevierViewall">A retrospective study showed that direct transplantation is at least non-inferior to pre-transplant cytoreduction and also avoids selection of resistant clones so that, in case of relapse, these patients would be candidates for salvage treatment with hypomethylating agents, with a higher probability of response and overall survival after relapse.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Some authors advocate the use of cytoreductive therapy in patients with > 10% blasts as this subgroup of patients has a higher post-transplant relapse rate. AML-type induction chemotherapy could provide good responses in terms of reducing the relapse rate, however, it has a non-negligible toxicity and mortality profile. On the other hand, hypomethylating agents have been shown to be effective in cytoreduction with a good safety profile.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Prospective studies are needed to help us establish the best pre-transplant strategy.</p><p id="par0255" class="elsevierStylePara elsevierViewall">As MDS is a disease with a higher incidence in older patients, multiple studies have been conducted to establish the efficacy of different conditioning regimens, including reduced-intensity conditioning. In young patients (18–60 years), transplantation with myeloablative conditioning provides the best quality-of-life adjusted survival. However, the > 60 years patient subgroup (higher prevalence of MDS) is not considered for this type of conditioning. A Markov decision model pointed towards reduced-intensity conditioning for MDS patients > 60 years over non-transplant strategies, as it had benefits in terms of life expectancy and quality of life assuming a higher probability of relapse.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Refractory to hypomethylating agents</span><p id="par0260" class="elsevierStylePara elsevierViewall">Hypomethylating agents are characterised by transient complete responses and may even progress to AML.</p><p id="par0265" class="elsevierStylePara elsevierViewall">A recent study by Prébet et al. showed that overall survival in patients refractory to hypomethylating agents is reduced to 6 months.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> The challenge in this subgroup of patients lies in the lack of effective therapeutic options after failure of hypomethylating agents.</p><p id="par0270" class="elsevierStylePara elsevierViewall">The choice of the best treatment should be based on additional data, such as the type of resistance to hypomethylating agents (primary versus secondary) or cytogenetic and molecular characteristics. Available options include allogeneic transplantation and intensive chemotherapy, both of which are limited to a small subset of patients. Therefore, given the limited options for these patients, there is a need to develop targeted clinical trials in this population.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p></span></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusion</span><p id="par0275" class="elsevierStylePara elsevierViewall">Despite advances in the diagnosis, classification and treatment of MDS, multiple challenges remain. The complexity and heterogeneity of the disease makes it difficult to design standardised therapeutic strategies and the lack of biological markers of response makes it difficult to choose the most appropriate therapy. Therefore, further studies are needed to understand MDS biology and to develop therapies that improve patients' quality of life.</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Ethical considerations</span><p id="par0280" class="elsevierStylePara elsevierViewall">The work is a review and does not involve the use of human subjects and therefore does not require informed consent.</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Funding</span><p id="par0285" class="elsevierStylePara elsevierViewall">AAP Juan Rodés Contracts "JR19/00011".</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflict of interest</span><p id="par0290" class="elsevierStylePara elsevierViewall">AAP: has received speaking fees from Novartis, BMS, Abbvie, Jazz Pharma, Janssen and Syros; has been involved in consultancy services for BMS, Syros, Jazz Pharma and Astellas; and has received research funding from AstraZeneca. MPI: no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Diagnosis" ] 2 => array:3 [ "identificador" => "sec0015" "titulo" => "Classification" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "World Health Organization classification 2022" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "International Consensus Classification 2022" ] ] ] 3 => array:3 [ "identificador" => "sec0030" "titulo" => "Prognosis" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Revised International Prognostic Scoring System" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "International Prognostic Scoring System Molecular" ] ] ] 4 => array:3 [ "identificador" => "sec0045" "titulo" => "Treatment" "secciones" => array:2 [ 0 => array:3 [ "identificador" => "sec0050" "titulo" => "Low-risk myelodysplastic neoplasms" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Erythropoiesis-stimulating agents" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Lenalidomide" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Luspatercept" ] 3 => array:2 [ "identificador" => "sec0070" "titulo" => "Allogeneic transplantation" ] ] ] 1 => array:3 [ "identificador" => "sec0075" "titulo" => "High-risk myelodysplastic neoplasms" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0080" "titulo" => "Hypomethylating agents" ] 1 => array:2 [ "identificador" => "sec0085" "titulo" => "Acute myeloid leukaemia-type chemotherapy" ] 2 => array:2 [ "identificador" => "sec0090" "titulo" => "Allogeneic transplantation" ] 3 => array:2 [ "identificador" => "sec0095" "titulo" => "Refractory to hypomethylating agents" ] ] ] ] ] 5 => array:2 [ "identificador" => "sec0100" "titulo" => "Conclusion" ] 6 => array:2 [ "identificador" => "sec0105" "titulo" => "Ethical considerations" ] 7 => array:2 [ "identificador" => "sec0110" "titulo" => "Funding" ] 8 => array:2 [ "identificador" => "sec0115" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-05-01" "fechaAceptado" => "2023-07-12" "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1574 "Ancho" => 2931 "Tamanyo" => 320945 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Treatment algorithm for myelodysplastic neoplasms. EPO: erythropoietin; HMA: hypomethylating agents.</p>" ] ] 1 => array:9 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Khoury et al.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>" "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">cnLOH: loss of heterozygosity without copy number alteration; IB: increased blasts; BM: bone marrow; WHO: World Health Organisation; MDS: myelodysplastic syndrome; PB: peripheral blood.</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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Blasts</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Cytogenetics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Mutations \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">BM \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PB \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">MDS with defining genetic alterations</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MDS with low blast count and isolated 5q deletion (MDS-5q)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5q deletion alone or with an alteration other than 7q or del7q monosomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MDS with low blasts count and mutated SF3B1 (MDS-SF3B1)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absence of del5q, monosomy 7 or complex karyotype \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SF3B1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MDS with biallelic inactivation of TP53 (MDS-biTP53)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><20% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><20% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Generally complex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Two or more TP53 mutations or a mutation with evidence of TP53 copy number loss or cnLOH \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">MDS, morphologically defined</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MDS low blast count</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Hypoplastic MDS</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MDS with increased blasts</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MDS-IB1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5−9% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2−4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MDS-IB2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10−19% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5−19% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MDS with fibrosis (MDS-f) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5−19% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2−19% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3442323.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Classification of MDS according to the WHO Classification of the year 2022.</p>" ] ] 2 => array:9 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Zeidan et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>" "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">AML: acute myeloblastic leukaemia; BM: bone marrow; NOS: Not Otherwise Specified; MDS: myelodysplastic syndrome; PB: peripheral blood.</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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dysplastic lines \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cytopenia \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cytosis<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Blasts in BM and PB \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cytogenetics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mutations \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MDS-SF3B1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><5% BM and <2% PB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any except del(5q) isolated, -7/del(7q), abn3q26.2 complex, or del(5q) complex. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SF3B1 (VAF ≥ 10%), without TP53 multi-hit and RUNX1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MDS-del(5q) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thrombocytosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><5% BM and <2% PB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Del(5q). There may be an additional one except -7/del(7q). \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any except TP53 multi-hit \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MDS NOS, without dysplasia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><5 % BM and <2 % PB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−7/del(7q) or -7/del(7q) or complex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any except TP53 multi-hit or SF3B1 (VAF ≥ 10 %) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MDS NOS, with dysplasia in one line \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><5% BM and <2% PB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any except those not meeting criteria for MDS-del/5q) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any except TP53 multi-hit; does not meet criteria of MDS-SF3B1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MDS NOS, with multi-line dysplasia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><5% BM and <2% PB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any except those not meeting criteria for MDS-del/5q) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any except TP53 multi-hit; does not meet criteria of MDS-SF3B1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MDS with excess blasts \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5−9% BM and 2−9% PB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anyone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any except TP53 multi-hit \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MDS/AML \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10−19% BM or PB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any except those AML-defining \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any except NPM1, bZIP CEBPA or TP53 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3442324.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Cytosis: leukocytes ≥ 13 × 10<span class="elsevierStyleSup">9</span>l, monocytes (≥0.5 × 10<span class="elsevierStyleSup">9</span> and ≥10% leukocytes) or platelets ≥450 × 10<span class="elsevierStyleSup">9</span>l.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Classification of the MDS according to the 2022 ICC.</p>" ] ] 3 => array:9 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Greenberg et al.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>" "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">BM: bone marrow; PMN: polymorphonuclears.</p>" "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">0 points \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">0.5 points \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">1 point \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">1.5 points \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2 points \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">3 points \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">4 points \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cytogenetic risk group<span class="elsevierStyleSup">a</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Very good \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Good \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intermediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Poor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Very poor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BM blasts, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0−2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3−4.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5−10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">> 10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Haemoglobin, g/dl \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8−9.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Platelets, × 10<span class="elsevierStyleSup">9</span>l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50−99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PMN, × 10<span class="elsevierStyleSup">9</span>l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="8" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risk groups: Very low: 0−1.5 points; Low: > 1.5−3 points; Intermediate: > 3−4.5 points; High: > 4.5−6 points; Very high: > 6 points.</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3442322.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cytogenetic risk categories<span class="elsevierStyleSup">a</span></th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Very good \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-Y, del(11q) isolated \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Good \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Normal, del(5q), del(12p) and del(20q) isolated and double anomalies including del(5q) (except with -7 or del(7q)) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intermediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">del(7q), + 8, + 19, isolated i(17q) and any other single or double anomalies in independent clones \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Poor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−7 and isolated inv(3)/t(3q)/del(3q), double anomalies including −7/del(7q) and complex anomalies with 3 anomalies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Very poor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complex anomalies with > 3 anomalies \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3442321.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Revised International Prognostic Scoring System.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and treatment of myelodysplastic syndromes: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.A. Sekeres" 1 => "J. 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