Original article
Clinico-biological characteristics of patients with myelofibrosis: an analysis of 1,000 cases from the Spanish Registry of Myelofibrosis
Características clínico-biológicas de los pacientes con mielofibrosis: un análisis de 1.000 casos del Registro Español de Mielofibrosis
Irene Pastor-Galána, Juan Carlos Hernández-Boludaa,b,
, Juan-Gonzalo Correac, Alberto Alvarez-Larránc,d, Francisca Ferrer-Maríne, José María Rayaf, Rosa Ayalag, Patricia Velezh, Manuel Pérez-Encinasi, Natalia Estradaj, Valentín García-Gutiérrezk, María Laura Foxl, Angel Payerm, Ana Kerguelenn, Beatriz Cuevaso, María Antonia Duránp, María José Ramírezq, María Teresa Gómez-Casaresr, María Isabel Mata-Vázquezs, Elvira Morat..., Clara Martínez-Valverdeu, Elisa Arbelov, Anna Angonaw, Elena Magrox, María Luisa Anteloy, Nieves Somolinosz, Francisco Cervantesc, on behalf of the Spanish Group of Philadelphia-Negative Myeloproliferative Diseases (GEMFIN) Ver más
Corresponding author
a Servicio de Hematología, Hospital Clínico Universitario-INCLIVA, Valencia, Spain
b Departamento de Medicina, Universidad de Valencia, Valencia, Spain
c Servicio de Hematología, Hospital Clínic-IDIBAPS, Universidad de Barcelona, Barcelona, Spain
d Servicio de Hematología, Hospital del Mar-IMIM, Barcelona, Spain
e Servicio de Hematología y Oncología Médica, Hospital Morales Meseguer-CIBERER, IMIB-Arrixaca, UCAM, Murcia, Spain
f Servicio de Hematología, Hospital Universitario de Canarias, Tenerife, Spain
g Servicio de Hematología, Hospital 12 de Octubre, Madrid, Spain
h Servicio de Hematología, Institut Català d’Oncologia, Hospital Duran i Reynals, Hospitalet de Llobregat, Barcelona, Spain
i Servicio de Hematología, Hospital Clínico Universitario, Santiago de Compostela, Spain
j Servicio de Hematología, Institut Català d’Oncologia-Hospital Germans Trias i Pujol, Instituto de Investigación Josep Carreras, Badalona, Spain
k Servicio de Hematología, Hospital Ramón y Cajal-IRYCIS, Madrid, Spain
l Servicio de Hematología, Hospital Vall d’Hebron, Barcelona, Spain
m Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain
n Servicio de Hematología, Hospital La Paz, Madrid, Spain
o Servicio de Hematología, Hospital Universitario de Burgos, Burgos, Spain
p Servicio de Hematología, Hospital Son Espases, Mallorca, Spain
q Servicio de Hematología, Hospital de Jerez, Jerez de la Frontera, Cádiz, Spain
r Servicio de Hematología, Hospital Dr Negrín, Las Palmas de Gran Canaria, Spain
s Servicio de Hematología, Hospital Costa del Sol, Marbella, Spain
t Servicio de Hematología, Hospital La Fe, IIS La Fe, Valencia, Spain
u Servicio de Hematología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
v Servicio de Hematología, Hospital Virgen de la Macarena, Sevilla, Spain
w Servicio de Hematología, Institut Català d’Oncologia, Hospital Josep Trueta, Girona, Spain
x Servicio de Hematología, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
y Servicio de Hematología, Complejo Hospitalario de Navarra, Pamplona, Spain
z Servicio de Hematología, Hospital Universitario de Getafe, Madrid, Spain
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Hospital Clínico Universitario-INCLIVA, Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Medicina, Universidad de Valencia, Valencia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Clínic-IDIBAPS, Universidad de Barcelona, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Hematología, Hospital del Mar-IMIM, Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Hematología y Oncología Médica, Hospital Morales Meseguer-CIBERER, IMIB-Arrixaca, UCAM, Murcia, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario de Canarias, Tenerife, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Servicio de Hematología, Hospital 12 de Octubre, Madrid, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Servicio de Hematología, Institut Català d’Oncologia, Hospital Duran i Reynals, Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Clínico Universitario, Santiago de Compostela, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Servicio de Hematología, Institut Català d’Oncologia-Hospital Germans Trias i Pujol, Instituto de Investigación Josep Carreras, Badalona, Spain" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Ramón y Cajal-IRYCIS, Madrid, Spain" "etiqueta" => "k" "identificador" => "aff0055" ] 11 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Vall d’Hebron, Barcelona, Spain" "etiqueta" => "l" "identificador" => "aff0060" ] 12 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain" "etiqueta" => "m" "identificador" => "aff0065" ] 13 => array:3 [ "entidad" => "Servicio de Hematología, Hospital La Paz, Madrid, Spain" "etiqueta" => "n" "identificador" => "aff0070" ] 14 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario de Burgos, Burgos, Spain" "etiqueta" => "o" "identificador" => "aff0075" ] 15 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Son Espases, Mallorca, Spain" "etiqueta" => "p" "identificador" => "aff0080" ] 16 => array:3 [ "entidad" => "Servicio de Hematología, Hospital de Jerez, Jerez de la Frontera, Cádiz, Spain" "etiqueta" => "q" "identificador" => "aff0085" ] 17 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Dr Negrín, Las Palmas de Gran Canaria, Spain" "etiqueta" => "r" "identificador" => "aff0090" ] 18 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Costa del Sol, Marbella, Spain" "etiqueta" => "s" "identificador" => "aff0095" ] 19 => array:3 [ "entidad" => "Servicio de Hematología, Hospital La Fe, IIS La Fe, Valencia, Spain" "etiqueta" => "t" "identificador" => "aff0100" ] 20 => array:3 [ "entidad" => "Servicio de Hematología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain" "etiqueta" => "u" "identificador" => "aff0105" ] 21 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Virgen de la Macarena, Sevilla, Spain" "etiqueta" => "v" "identificador" => "aff0110" ] 22 => array:3 [ "entidad" => "Servicio de Hematología, Institut Català d’Oncologia, Hospital Josep Trueta, Girona, Spain" "etiqueta" => "w" "identificador" => "aff0115" ] 23 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain" "etiqueta" => "x" "identificador" => "aff0120" ] 24 => array:3 [ "entidad" => "Servicio de Hematología, Complejo Hospitalario de Navarra, Pamplona, Spain" "etiqueta" => "y" "identificador" => "aff0125" ] 25 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario de Getafe, Madrid, Spain" "etiqueta" => "z" "identificador" => "aff0130" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Características clínico-biológicas de los pacientes con mielofibrosis: un análisis de 1.000 casos del Registro Español de Mielofibrosis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1559 "Ancho" => 1528 "Tamanyo" => 70674 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Overall survival of the series of 1000 patients with myelofibrosis.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by a clonal expansion of hematopoietic stem cells that is accompanied by medullary fibrosis and extramedullary haematopoiesis, mainly in the spleen and liver.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> MF may develop <span class="elsevierStyleItalic">de novo</span> (Primary MF, PMF) or be secondary (SMF) to the progression of essential thrombocythemia (post-ET MF) or polycythaemia vera (post-PV MF). It is a rare disease, with an incidence of between 0.1 and 1 new cases per 100,000 inhabitants per year.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The discovery of the key role of activation of the JAK2-STAT signalling pathway in MF has been a breakthrough for understanding the pathogenesis of the disease and the development of new treatments.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Thus, most patients have activating mutations of this pathway in genes <span class="elsevierStyleItalic">JAK2</span> (∼60%), of calreticulin (<span class="elsevierStyleItalic">CALR</span>, ∼20–25%) or of the thrombopoietin receptor (<span class="elsevierStyleItalic">MPL,</span> ∼5–10%). In about 10% of the patients it is not possible to detect mutations of the previous genes. These are known as the “triple negatives”. More recently, additional somatic mutations have been demonstrated in more than half of MF patients, some of which appear to determine the prognosis of the disease.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">MF generally affects the elderly and has a very heterogeneous clinical course, characterized by the occurrence of anaemia, symptomatic splenomegaly, and constitutional symptoms. Approximately 15–20% of patients develop acute leukaemia over time, a situation that is associated with a poor prognosis.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The survival of patients with MF varies greatly depending on the presence or absence of adverse prognostic factors, with a median of about 6 years.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Allogeneic hematopoietic stem-cell transplantation is the only curative therapy for MF, but it is associated with high morbidity and mortality.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> For this reason, it is crucial to determine which patients may be candidates for this procedure based on their age, general condition, and predictable survival according to the prognostic MF indices.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> However, in clinical practice, most patients are not candidates for transplantation and their treatment is aimed at symptom control.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In this sense, the therapeutic outlook of MF has improved substantially in recent years with the introduction of JAK2 inhibitors, highly effective drugs for the control of hyperproliferative manifestations of the disease, such as splenomegaly or constitutional symptoms.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The objective of the present study was to describe the clinical-biological characteristics, the treatment, the course and the utility of the prognostic indices in patients with MF in Spain.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">The Spanish Registry of Myelofibrosis (GEM-MIE-2014-01) is a national database that contains anonymised clinical information of patients with PMF or SMF diagnosed since 2000 in hospitals affiliated to the Spanish Group of Philadelphia-Negative Myeloproliferative Diseases (GEMFIN). Patients must sign the corresponding informed consent prior to their inclusion in the registry.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The diagnosis of MF was made in each center based on the current valid criteria at the beginning of the disease, without a centralized histological review. The prognostic classification of patients at the time of diagnosis was based on the <span class="elsevierStyleItalic">International Prognosis Scoring System</span> (IPSS),<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> which defines 4 risk categories (low, intermediate-1, intermediate-2 and high) based on 5 clinical variables: age >65 years, constitutional symptoms (weight loss, sweating, low-grade fever), haemoglobin (Hb)<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>g/dl, leukocytes<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>25<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l and circulating blasts<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>1%. The <span class="elsevierStyleItalic">Myelofibrosis Secondary to PV and ET Prognostic Model</span> (MYSEC-PM)<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> was applied in patients with SMF, a recent prognostic model based on 6 clinical-biological variables: age, constitutional symptoms, Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>g/dl, thrombocytopenia<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>150<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l, circulating blasts<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>3% and the <span class="elsevierStyleItalic">CALR</span> gene mutation status.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The quantitative variables were expressed using the median and the interquartile range (IQR) and the qualitative ones using percentages. Differences in the distribution of categorical and continuous variables were analysed using the Chi square test and the Mann-Whitney U test, respectively. The Kaplan-Meier method was used for the survival analysis and the log-rank test for comparisons. Survival was defined as the time from diagnosis to death or date of last visit. P values<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 were considered statistically significant. The incidence of leukaemia and vascular complications was calculated by the number of events per 100 patient-years of follow-up. Major bleeding was defined as any clinically significant bleeding according to medical criteria or that associated with a decrease in Hb of at least 2<span class="elsevierStyleHsp" style=""></span>g/dl with or without transfusion requirement. The Fine & Gray method was used to calculate the cumulative incidence of leukaemia, taking into account the competitive risks. Statistical analysis was performed using IBM SPSS 22.0 and R software.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">From January 2000 to January 2017, clinical data were included in the Spanish Myelofibrosis Registry for a total of 1000 adult patients with PMF (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>641) or post-ET MF (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>216) or post-PV MF (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>143) from 61 Spanish hospitals. The median age of the series at the time of diagnosis was 68 years (IQR: 60−76), with 59% of patients older than 65 years and a male predominance (60%). The majority (62%) developed some cardiovascular risk factor and 96 patients (10%) had a thrombotic history. Thrombosis was detected in 14 cases coinciding with the diagnosis of MF. A third of the patients reported constitutional symptoms and 8% pruritus. Physical examination revealed palpable splenomegaly in 81% of patients, this being greater than 10<span class="elsevierStyleHsp" style=""></span>cm below the costal margin in 22% of cases. All in all, only 17% of patients reported discomfort related to splenomegaly. Regarding the laboratory values at diagnosis, the median value of Hb was 10.7<span class="elsevierStyleHsp" style=""></span>g/dl (IQR: 9.2–12.5) and 36% of the series had moderate or severe anaemia (Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>g/dl). The frequency of moderate-severe anaemia was higher in patients with constitutional symptoms than in the rest (46 vs. 31%, p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). Median white blood cell count was 9.9<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l (IQR: 5.9–16.6), with 11% of cases being<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>25<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l. Forty-five percent of the patients had at least 1% of blast cells in the peripheral blood smear, with this value being >3% in 12% of the series. The median platelet count was 304<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l (IQR: 150–519), with this count being <100<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l and <50<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l in 15% and 6% of cases, respectively. The frequency of marked thrombocytopenia (<50<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l) was similar in patients with massive splenomegaly (>10<span class="elsevierStyleHsp" style=""></span>cm under costal margin) than in the rest (5.4 vs. 6%, respectively; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.75). Regarding the pattern of spinal biopsy, 13% had medullary osteosclerosis. An assessable cytogenetic study was only obtained in 515 patients; of these, cytogenetic abnormalities were reported in 29% of cases. Twelve percent of patients had an unfavourable karyotype.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Finally, the profile of driver mutations was <span class="elsevierStyleItalic">JAK2</span>-mutated (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>569; 57%), <span class="elsevierStyleItalic">CALR</span>-mutated (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>113, 11%), <span class="elsevierStyleItalic">MPL</span>-mutated (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11, 1%), triple negative (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>49.5%) and uncharacterized (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>258, 26%). <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the comparison of the baseline clinical-biological characteristics of the patients with PMF and SMF. The molecular characterization of patients with post-ET MF and post-PV MF can be seen in Appendix B Table S1 of the additional material.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Treatment</span><p id="par0050" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the list of treatments used depending on the period of diagnosis of MF. As can be seen, hydroxyurea was the most frequently used cytoreductive agent. However, as of 2010, the number of patients treated with ruxolitinib progressively increased. In contrast, the use of interferon was minimal in our environment. Likewise, the indication of splenectomy (2%) or irradiation of the spleen (2%) was uncommon. Erythropoietic agents (35%) and danazol (14.5%) were the most commonly used drugs to treat anaemia. The use of immunomodulatory agents has been decreasing and these drugs are rarely used nowadays in clinical practice. A small number of patients (5%) received corticosteroids for the management of anaemia or thrombocytopenia. Finally, 75 patients in the series (7.5%) received an allogeneic hematopoietic stem-cell transplantation. Median age at transplant was 56 years (extremes, 28–69). Most of the transplanted patients (73 cases of the total) had been diagnosed with FM <65 years of age.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Progression complications, survival and risk groups</span><p id="par0055" class="elsevierStylePara elsevierViewall">The median follow-up of living patients was 35 months (IQR: 16–64). At the time of analysis, 424 patients (42%) had died; the causes of death were (known in 381 cases): progression of MF (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>88; 23%), leukaemia (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>87; 23%), cardiorespiratory failure (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>fifty; 13%), infection (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>fifty; 13%), transplant complications (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>30; 8%), bleeding (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>24; 6%), thrombosis (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>16; 4%), secondary neoplasm (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>15; 4%), liver failure (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6; 2%) and other causes (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>15; 4%).</p><p id="par0060" class="elsevierStylePara elsevierViewall">During the observation period, 68 patients (7%) developed a total of 71 thrombotic complications (44 arterial, 27 venous), with an incidence of 1.96 events per 100 patient-years. On the other hand, 106 patients (11%) developed some bleeding complication (49 minor, 57 major). The incidence of major bleeding was 1.6 episodes per 100 patient-years. A total of 97 patients (10%) developed acute leukaemia, which corresponds to an incidence of 2.7 cases per 100 patient-years. The cumulative incidence of leukaemia at 10 years was 15% (95% CI: 12–18) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). On the other hand, 44 patients were diagnosed with a second malignancy after the diagnosis of MF (skin: 12, gastrointestinal: 11, urothelial: 4, breast: 3, lung: 2, pancreas: 2, larynx: 1, uterus: 1, prostate: 1, lymphoma: 1, bone metastases of unknown primary origin: 1, origin not indicated: 5). Appendix B Table S2 of the additional material shows the sequence and duration of the drugs received in the 15 patients who died of secondary malignancies.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The median survival of the series was 5.7 years (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). There were no statistically significant differences in the survival of patients with PMF or SMF (median of 5.7 vs. 6.6 years, respectively; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.98) (Additional material Appendix B Fig. S1). However, the survival of patients with post-PT MF was significantly greater than that of those with post-PV MF (7.4 vs. 3.7 years, respectively; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.013) (Additional material Appendix B Fig. S2). The association between the 5 IPSS variables with survival was statistically significant (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 for all of them). The application of this prognostic index in the global series allowed us to identify 4 clearly differentiated risk groups (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Thus, median survival was not achieved in the low-risk group (12% of the total), while it was 8.8 years; 5.3 years and 2.8 years in the intermediate-1 (26%), intermediate-2 (32%) and high-risk (30%) groups, respectively. Apart from the clinical variables integrated in the IPSS, the mutational profile was also associated with the prognosis. Thus, the 5-year survival probability of the 113 patients with a <span class="elsevierStyleItalic">CALR</span> gene mutation was significantly higher than that of the rest of the cases characterized at molecular level (88 vs. 58%, p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). Finally, the new prognostic index MYSEC-PM was applied in the 265 patients with SMF for whom the necessary information was available. This model allowed stratifying patients into 4 risk groups (Additional material Appendix B Fig. S3) Thus, the median survival was not reached in the low-risk group (19% of the total), with 7.7 years, 3.4 years and 1.7 years in the intermediate-1 (40%), intermediate-2 (26%) and high-risk (15%) risk categories, respectively.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">The present study describes the clinical-biological characteristics, the clinical course and the treatment of 1000 patients with MF from 61 Spanish hospitals. It should be noted that this work analyses the largest national multicenter series of patients with this disease.</p><p id="par0075" class="elsevierStylePara elsevierViewall">First, the study shows that MF is a disease of the elderly (median of 68 years), where only 10% of patients are under the age of 50 at the time of diagnosis. In published series from reference centres, the median age of patients with PMF<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> or SMF<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> (64 years in both) is somewhat younger than ours, which could reflect the referral of younger patients to these centres in search of more specialized treatments. On the other hand, this analysis allows identifying the main clinical problems of FM<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>: anaemia (36% of patients with Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>g/dl), constitutional symptoms (35%,with the most common being weight loss) and splenomegaly-related discomfort (17%). Many patients experience several symptoms concomitantly (e.g., almost half of the patients with constitutional symptoms had moderate/severe anaemia), making their therapeutic management difficult. Although it has not been included in the present study, the frequency of these manifestations, especially of the anaemic syndrome, increases during the course of the disease.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The proportion of patients with PMF (2 thirds of the total) was somewhat higher than that reported in clinical trials,<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,14</span></a> but is in line with that of other series.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In general, the clinical profile of disease presentation was similar in patients with PMF or SMF. However, while there was a male predominance in PMF and post-PV MF (67% and 54% of men, respectively), this was not the case in post-ET MF (56% were women). Furthermore, weight loss, moderate or severe anaemia and thrombocytopenia was less common in patients with SMF. Another notable difference is that patients with post-PV MF almost always have the <span class="elsevierStyleItalic">JAK2</span> gene mutated (100% in our series), while the frequency of this mutation in patients with post-ET PMF and MF was 75% and 53%, respectively.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Regarding treatment, the results confirm that the majority of MF patients receive treatments aimed at symptom control. Despite the fact that transplantation is the only curative treatment for FM and its indication is growing according to data from international registries,<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17</span></a> only 7.5% of the patients in our series were transplanted, a percentage similar to that of reference centres in this disease.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a> It should be said that the proportion of transplant patients rose to 18% among those diagnosed with FM under 65 and therefore, <span class="elsevierStyleItalic">a priori</span>, best candidates for the procedure. In any case, a poor general condition, comorbidities or the perception of the high risk of transplant complications by the doctor and/or the patient are factors that limit the indication for transplantation in this disease. Among the treatments aimed at improving anaemia, the wide use of erythropoietic agents stands out (35% of the series). As we already published in previous studies of the group, the administration of these drugs in patients with erythropoietin serum levels inadequate for the degree of anaemia allows responses to be obtained in about half of the cases, with a median duration of one and a half years.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Other less frequently used anaemia treatments were danazol,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> corticosteroids<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and immunomodulatory agents, the latter increasingly in decline. For the control of symptoms and splenomegaly, it is worth noting the emergence of ruxolitinib in clinical practice, a drug that has represented the most important advance in the management of FM in recent years. However, the worsening of cytopenia during ruxolitinib treatment is an unresolved clinical problem, perhaps through the combined use of drugs or the use of new JAK2 inhibitors that do not cause thrombocytopenia.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Median survival in our series was closed to 6 years, suggesting that MF significantly shortens patients’ life expectancy.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Overall, we observed no difference in survival between PMF or SMF patients, although the post-ET MF subgroup had a median survival of 7.4 years. IPSS allowed to identify 4 clearly differentiated risk groups in the global series. The intermediate-2 and high-risk groups (62% of the total) would have an estimated median survival of 5.3 years and 2.8 years, respectively, which would make them potential transplant candidates according to current expert recommendations.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Integration of IPSS together with additional molecular information (favourable impact of <span class="elsevierStyleItalic">CALR</span> gene mutations and unfavourable of “triple negativity” or high-risk somatic mutations) may help to better profile transplant candidates.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,24</span></a> On the other hand, the IPSS was designed from PMF patient data and does not effectively discriminate the risk groups in the SMF.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> For this reason, a specific model for SMF has recently been proposed, the MYSEC-PM.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> As we have been able to verify with the registry data, this model is more discriminative than the IPSS in the SMF, but in it the age probably has an excessive importance. In this way, the MYSEC-PM high-risk group is made up almost exclusively of patients over the age of 70, which makes it less useful when selecting candidates for transplantation.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The most common causes of death in our series were clinical deterioration derived from MF and leukemic transformation. Unfortunately, there is currently no drug available that can decrease the risk of leukaemia associated with MF (15% at 10 years). Other common causes of death were infections and vascular complications (hemorrhagic and thrombotic). In this sense, it should be noted that, although the incidence of thrombosis in MF is similar to that of ET,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> there are no consensus recommendations on how to prevent this complication.</p><p id="par0100" class="elsevierStylePara elsevierViewall">The Spanish Myelofibrosis Registry has various limitations. The quality of the data depends on the treating haematologist, without external monitoring. The entry of cases is highly variable from one center to another and is generally unrelated to the size of their healthcare area, which prevents us from knowing the incidence or prevalence of FM in our environment. Characterization of the basic molecular profile is absent in a quarter of the included patients. Unfortunately, the registry does not have public funding for its maintenance. However, the high number of patients included in the registry (currently there are approximately 1300 cases) allows obtaining a representative sample of the disease not subject to the selection biases of clinical trials. Registration is a useful tool to define or validate prognostic models<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25,26</span></a> and analyse the results of treatment in healthcare practice.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20,22</span></a> Over time, it will allow to identify changes in patient treatment guidelines, as well as the potential benefit in their survival.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of interests</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1376976" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1264651" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1376977" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1264650" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0020" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Treatment" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Progression complications, survival and risk groups" ] ] ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interests" ] 9 => array:2 [ "identificador" => "xack478460" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-08-30" "fechaAceptado" => "2019-11-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1264651" "palabras" => array:6 [ 0 => "Myelofibrosis" 1 => "Prognosis" 2 => "Treatment" 3 => "Myeloproliferative neoplasms" 4 => "Spanish registry of myelofibrosis" 5 => "Transplantation" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1264650" "palabras" => array:6 [ 0 => "Mielofibrosis" 1 => "Pronóstico" 2 => "Tratamiento" 3 => "Neoplasias mieloproliferativas" 4 => "Registro español de mielofibrosis" 5 => "Trasplante" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Myelofibrosis is an infrequent chronic myeloproliferative neoplasm. We aimed to describe the clinico-biological characteristics, treatment, and evolutive course of myelofibrosis patients in Spain.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">A total of 1000 patients from the Spanish Registry of Myelofibrosis diagnosed with primary (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>641) or secondary (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>359) myelofibrosis were analysed.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Median age was 68 years. The frequency of constitutional symptoms, moderate to severe anaemia (Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>g/dL), and symptomatic splenomegaly was 35%, 36%, and 17%, respectively. The rate of thrombosis and haemorrhage was 1.96 and 1.6 events per 100 patient-years, respectively. The cumulative incidence of leukaemia at 10 years was of 15%. The most frequent therapies for the anaemia were the erythropoiesis stimulating agents and danazol. From 2010, a progressive increase in the use of ruxolitinib was noticed. A total of 7.5% of patients were transplanted. During the observation period, 42% of patients died mainly due to the clinical deterioration caused by myelofibrosis or leukaemic transformation. The median survival of the series was 5.7 years. Four different risk categories were identified by the IPSS: median survival was not reached in the low risk group and was 8.8 years, 5.3 years, and 2.8 years in the intermediate-1, intermediate-2, and high-risk groups, respectively.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Myelofibrosis is a disabling condition mainly affecting elderly people. Its treatment is mostly driven by symptom control. Despite its clinical heterogeneity, several prognostic models are useful to select candidates for transplantation.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivo</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">La mielofibrosis es una neoplasia mieloproliferativa crónica infrecuente. Nuestro objetivo fue describir las características clínico-biológicas, el tratamiento y el curso evolutivo de los pacientes con mielofibrosis en España.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se analizaron 1.000 pacientes del Registro Español de Mielofibrosis diagnosticados de mielofibrosis primaria (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>641) o secundaria (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>359).</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">La mediana de edad era de 68 años. La frecuencia de sintomatología constitucional, anemia moderada o severa (Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>g/dl) y esplenomegalia sintomática fue del 35%, 36% y 17%, respectivamente. La incidencia de trombosis y hemorragia fue de 1,96 y 1,6 eventos por 100 años-paciente, respectivamente. La incidencia acumulada de leucemia fue del 15% a los 10 años. Para la anemia se emplearon principalmente agentes eritropoyéticos y danazol. A partir del 2010 se observó un incremento significativo del uso de ruxolitinib. Un 7,5% de los pacientes fue trasplantado. El 42% de los enfermos falleció, debido principalmente al deterioro clínico provocado por la mielofibrosis y a la transformación leucémica. La supervivencia mediana de la serie fue de 5,7 años. El IPSS identificó 4 grupos de riesgo: la supervivencia mediana no se alcanzó en el de bajo riesgo, mientras que fue de 8,8 años, 5,3 años y 2,8 años en los de riesgo intermedio-1, intermedio-2 y alto, respectivamente.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La mielofibrosis es una enfermedad invalidante que afecta sobre todo a personas de edad avanzada y cuyo tratamiento es fundamentalmente sintomático. A pesar de su heterogeneidad clínica se dispone de modelos pronósticos útiles para la selección de candidatos a trasplante.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as: Pastor-Galán I, Hernández-Boluda JC, Correa J-G, Alvarez-Larrán A, Ferrer-Marín F, Raya JM, et al. Características clínico-biológicas de los pacientes con mielofibrosis: un análisis de 1.000 casos del Registro Español de Mielofibrosis. Med Clin (Barc). 2020;155:152–158.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0120" class="elsevierStylePara elsevierViewall">The following are Supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia><elsevierMultimedia ident="upi0015"></elsevierMultimedia><elsevierMultimedia ident="upi0020"></elsevierMultimedia><elsevierMultimedia ident="upi0025"></elsevierMultimedia><elsevierMultimedia ident="upi0030"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0050" ] ] ] ] "multimedia" => array:11 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1016 "Ancho" => 1443 "Tamanyo" => 43100 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cumulative incidence of acute leukaemia in a series of 1,000 patients with myelofibrosis.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1559 "Ancho" => 1528 "Tamanyo" => 70674 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Overall survival of the series of 1000 patients with myelofibrosis.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1555 "Ancho" => 1514 "Tamanyo" => 151990 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Survival probability curves according to the risk groups defined by the IPSS in 1000 patients with myelofibrosis.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In bold: statistically significant values (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05).</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">Variable \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">PMF (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>641) \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">SMF (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>359) \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">p \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"><span class="elsevierStyleItalic">Age at diagnosis, years</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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">68 (60−76) \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">68 (57−75) \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">0.1 \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">Male sex, n (%)</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">427 (67) \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">172 (48) \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"><span class="elsevierStyleBold"><0001</span> \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">Constitutional symptoms, n (%)</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">235 (37) \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">113 (31.5) \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">0.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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>Profuse sweating, n (%) \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">74 (12) \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">42 (12) \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></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>Weight loss, n (%) \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">154 (25.5) \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">66 (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"><span class="elsevierStyleBold">0045</span> \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>Fever, n (%) \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">40 (7) \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">22 (7) \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></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">Palpable splenomegaly, n (%)</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">502 (80) \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">289 (81) \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">0.7 \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>>10<span class="elsevierStyleHsp" style=""></span>cm under costal margin, n (%)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">134 (22) \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">74 (22) \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></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">Palpable hepatomegaly, n (%)</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">145 (23) \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">70 (19.5) \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">0.3 \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">Haemoglobin, g/dl</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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">107 (9−12,5) \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">10.7 (9.6−12.2) \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">0.3 \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><10<span class="elsevierStyleHsp" style=""></span>g/dl, n (%)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">243 (39) \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">111 (32) \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"><span class="elsevierStyleBold">0044</span> \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><8<span class="elsevierStyleHsp" style=""></span>g/dl, n (%)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">82 (13) \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 (6) \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"><span class="elsevierStyleBold"><0001</span> \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">White blood cells, ×10</span><span class="elsevierStyleSup">9</span><span class="elsevierStyleItalic">/l</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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">9.5 (5.7−16.1) \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">10.6 (6−17.7) \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></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>>25<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l, n (%)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">67 (11) \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">39 (11) \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">0.7 \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">Circulating blasts, %</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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 (0−1) \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">0 (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">0.2 \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>≥<span class="elsevierStyleHsp" style=""></span>1%, n (%)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">267 (43.5) \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">162 (48.5) \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">0.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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">Platelets, ×<span class="elsevierStyleHsp" style=""></span>10</span><span class="elsevierStyleSup">9</span><span class="elsevierStyleItalic">/l</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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">276 (131−500) \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">342 (200−545) \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"><span class="elsevierStyleBold">0.012</span> \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><100<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l, n (%)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">114 (18) \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">35 (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"><span class="elsevierStyleBold">0.001</span> \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><<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l, n (%)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">44 (7) \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">16 (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">0.2 \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">High LDH, n (%)</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">558 (91) \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">304 (93) \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">0.3 \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">Cholesterol <150<span class="elsevierStyleHsp" style=""></span>mg/dl, n (%)</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">265 (56) \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">139 (56) \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></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">Serum erythropoietin <125<span class="elsevierStyleHsp" style=""></span>mU/mL, n (%)</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">249 (75) \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">147 (83) \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"><span class="elsevierStyleBold">0.046</span> \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">Cytogenetic abnormalities, n (%)</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">106 (30.5) \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">41 (25) \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></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">Adverse cytogenetics, n (%)</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">45 (14) \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">13 (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">0.1 \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="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Molecular profile, n (%)</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a></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><span class="elsevierStyleItalic">JAK2</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">359 (56) \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">210 (58) \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><span class="elsevierStyleItalic">CALR</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">55 (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">58 (16) \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><span class="elsevierStyleItalic">MPL</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">8 (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">3 (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"> \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>Triple negative \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">39 (6) \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 (3) \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>Not characterized \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">180 (28) \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">78 (22) \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 => "xTab2364202.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Median (interquartile range).</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Percentages on the number of cases with available information.</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">All polycythaemia (PV) patients who developed MF had the <span class="elsevierStyleItalic">JAK2</span> gene mutated.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Comparison of baseline clinical-biological characteristics of patients with primary (PMF) and secondary (SMF) myelofibrosis due to thrombocythemia or polycythaemia vera.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">In bold: statistically significant values (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05).</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">Treatment \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">2000–2009 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>430) \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">2010–2016 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>570) \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">p \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"><span class="elsevierStyleItalic">Median follow-up, months</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">63 \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">22 \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"><span class="elsevierStyleBold"><0.001</span> \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">Hydroxyurea, n (%)</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">265 (62) \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">270 (47) \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"><span class="elsevierStyleBold"><0.001</span> \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">Interferon, n (%)</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">8 (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">7 (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">0.4 \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">Immunomodulators, n (%)</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">59 (14) \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">19 (3) \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"><span class="elsevierStyleBold"><0.001</span> \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>Thalidomide, n (%) \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">23 (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">10 (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"><span class="elsevierStyleBold">0.002</span> \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>Lenalidomide, n (%) \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">37 (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">9 (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"><span class="elsevierStyleBold"><0.001</span> \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">Erythropoietic agents, n (%)</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">154 (36) \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">200 (35) \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></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">Danazol, n (%)</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">85 (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">60 (10.5) \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"><span class="elsevierStyleBold"><0.001</span> \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">Corticosteroids, n (%)</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 (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">28 (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">0.9 \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">JAK2 <span class="elsevierStyleItalic">inhibitors, n (%)</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">56 (13) \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">176 (31) \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"><span class="elsevierStyleBold"><0.001</span> \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>Ruxolitinib \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">54 (13) \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">172 (30) \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"><span class="elsevierStyleBold"><0.001</span> \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">Splenectomy, n (%)</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">12 (3) \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">12 (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">0.5 \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">Splenic irradiation, n (%)</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">16 (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">4 (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"><span class="elsevierStyleBold">0.001</span> \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">Autologous transplantation, n (%)</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">34 (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">41 (7) \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">0.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2364203.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">List of treatments administered to patients according to the diagnosis period of myelofibrosis.</p>" ] ] 5 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.docx" "ficheroTamanyo" => 21437 ] ] 6 => array:5 [ "identificador" => "upi0010" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc2.docx" "ficheroTamanyo" => 24752 ] ] 7 => array:5 [ "identificador" => "upi0015" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc3.docx" "ficheroTamanyo" => 25916 ] ] 8 => array:5 [ "identificador" => "upi0020" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "mmc4.jpeg" "Alto" => 1501 "Ancho" => 1417 "Tamanyo" => 96871 ] ] ] 9 => array:5 [ "identificador" => "upi0025" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "mmc5.jpeg" "Alto" => 1472 "Ancho" => 1417 "Tamanyo" => 117038 ] ] ] 10 => array:5 [ "identificador" => "upi0030" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "mmc6.jpeg" "Alto" => 1478 "Ancho" => 1417 "Tamanyo" => 101163 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:27 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathogenesis of myelofibrosis with myeloid metaplasia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. 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The current list of participants in the registry can be seen in the Supplementary material of this article, available online (Additional material Appendix B Table S3).</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015500000004/v2_202008242222/S2387020620302904/v2_202008242222/en/main.assets" "Apartado" => array:4 [ "identificador" => "43310" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015500000004/v2_202008242222/S2387020620302904/v2_202008242222/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020620302904?idApp=UINPBA00004N" ]
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