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El diagn&#243;stico se hizo seg&#250;n los criterios de la <span class="elsevierStyleItalic">World Health Organization</span> &#40;WHO&#41;-<span class="elsevierStyleItalic">European Organization of Research and Treatment of Cancer</span> &#40;EORTC&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">2</span></a>&#46; Se recogieron datos demogr&#225;ficos &#40;edad&#44; sexo&#44; subtipo diagn&#243;stico&#44; estado &#250;ltimo control&#41;&#44; estadio al diagn&#243;stico y a la progresi&#243;n &#40;la estadificaci&#243;n TNMB se realiz&#243; de acuerdo con el propuesto por la <span class="elsevierStyleItalic">International Society for Cutaneous Lymphoma</span> &#91;ISLC&#93; &#8211; EORTC&#41;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">4</span></a>&#44; par&#225;metros histol&#243;gicos &#40;transformaci&#243;n a c&#233;lula grande &#91;TCG&#93;&#44; foliculotropismo &#91;FT&#93;&#44; porcentaje de c&#233;lulas CD30&#43;&#44; Ki-67&#44; receptor de c&#233;lulas T &#91;TCR&#93; clonal en piel&#41; y par&#225;metros hematol&#243;gicos &#40;LDH&#44; beta2-microglobulina &#91;B2M&#93;&#44; leucocitos&#44; linfocitos&#44; TCR clonal en sangre&#41;&#46; La tinci&#243;n Ki-67 se consider&#243; intensa en aquellas biopsias que expresaron un &#237;ndice de proliferaci&#243;n Ki-67 mayor del 30&#37; y leve en aquellas en las que fue menor del 30&#37;&#46; En cuanto a la LDH y la B2M&#44; se consideraron elevadas si los valores eran mayores de 213<span class="elsevierStyleHsp" style=""></span>U&#47;L y 2&#44;4<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; respectivamente&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Se consider&#243; TCG cuando la presencia de linfocitos grandes exced&#237;a m&#225;s del 25&#37; del infiltrado d&#233;rmico o por la formaci&#243;n de n&#243;dulos de c&#233;lulas grandes<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">La PFS se defini&#243; como el tiempo desde la primera respuesta objetiva al tratamiento hasta la recidiva&#44; progresi&#243;n o fallecimiento &#40;en los pacientes que progresan&#41; o hasta la fecha del &#250;ltimo control &#40;en los pacientes sin progresi&#243;n&#41;&#59; la supervivencia global &#40;<span class="elsevierStyleItalic">overall survival</span> &#91;OS&#93;&#41;&#44; desde la fecha de inicio del tratamiento hasta la fecha de fallecimiento por cualquier causa&#59; y la DSS&#44; desde la fecha del inicio del tratamiento hasta la fecha de fallecimiento a consecuencia del linfoma&#46; Se defini&#243; progresi&#243;n como el cambio de un estadio a otro superior&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lisis estad&#237;stico</span><p id="par0030" class="elsevierStylePara elsevierViewall">Se utilizaron an&#225;lisis y gr&#225;ficos con el software SPSS Statistics para el an&#225;lisis estad&#237;stico&#46; Se realiz&#243; un an&#225;lisis descriptivo de frecuencias para variables categ&#243;ricas y se evalu&#243; la normalidad de las variables num&#233;ricas&#46; Se emplearon tablas de contingencia y pruebas estad&#237;sticas para analizar relaciones entre variables&#46; Se aplic&#243; la prueba de Fisher o la prueba de Ji-Cuadrado seg&#250;n correspondiera&#44; dependiendo del tama&#241;o de las frecuencias esperadas&#46; Se realizaron an&#225;lisis U de Mann-Whitney para comparar variables num&#233;ricas con categ&#243;ricas&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Se estim&#243; la DSS y tasas de supervivencia a diferentes a&#241;os utilizando el m&#233;todo de Kaplan-Meier&#46; Se aplic&#243; la prueba de Log-Rank para comparar grupos&#46; Se llevaron a cabo an&#225;lisis multivariantes utilizando el modelo de regresi&#243;n de riesgos proporcionales de Cox&#44; incluyendo variables significativas de an&#225;lisis previos&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><p id="par0040" class="elsevierStylePara elsevierViewall">Se incluyeron un total de 148 casos&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se describen las caracter&#237;sticas principales de los pacientes con MF y SS&#46; La mediada de edad fue de 62 a&#241;os &#91;49-70 a&#241;os&#93;&#44; con un 63&#37; de hombres&#46; Ciento veinti&#250;n casos &#40;82&#37;&#41; fueron diagnosticados de MF y 27 casos de SS&#46; Al diagn&#243;stico&#44; los estadios iniciales &#40; <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se incluye tambi&#233;n los resultados del an&#225;lisis univariante Kaplan-Meier&#47;Log-Rank de supervivencia espec&#237;fica de la cohorte para cada una de las variables que a continuaci&#243;n se detallan&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">En el an&#225;lisis univariante&#44; la edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os &#40;52&#37; de los casos&#41; se asoci&#243; a una peor DSS con una media de supervivencia de 121 meses&#46; No se encontraron diferencias en funci&#243;n del sexo&#46; En cuanto al diagn&#243;stico&#44; el SS present&#243; peor evoluci&#243;n con una media de supervivencia de 86&#44;6 meses y una probabilidad de supervivencia a los 5 a&#241;os del 50&#37;&#44; comparado con el 88&#37; en el grupo de MF &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>A&#41;&#46; No obstante&#44; no se encontraron diferencias en cuanto a supervivencia comparando los pacientes con SS frente al grupo de las MF avanzadas&#46; Respecto al estadio al diagn&#243;stico&#44; en la <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>B se indica la media de DSS y la probabilidad de supervivencia a 1&#44; 3 y 5 a&#241;os para cada estadio&#46; No se observaron diferencias estad&#237;sticamente significativas entre el estadio I y III&#44; pero s&#237; se observaron diferencias al compararlo con el estadio IIB y IVA&#46; Respecto al estadio IVA&#44; que incluye el IVA1 con afectaci&#243;n en sangre perif&#233;rica B2 &#40;mediana DSS 55 meses&#41; y IVA2 en el caso de pacientes con afectaci&#243;n ganglionar N3 &#40;mediana DSS 14 meses&#41;&#44; no se encontraron diferencias entre ambos grupos&#46; Sin embargo&#44; al comparar la supervivencia de N3 y&#47;o Nx &#40;ganglios perif&#233;ricos an&#243;malos sin confirmaci&#243;n histol&#243;gica&#41; con la de N1 y&#47;o N2 s&#237; se evidenciaron diferencias&#46; Tambi&#233;n se encontraron diferencias en la supervivencia entre los pacientes con afectaci&#243;n B2 &#40;IVA&#41;&#44; que mostraron un peor pron&#243;stico &#40;62&#44;6 vs&#46; 146&#44;5 meses&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; que aquellos con B0 o B1&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">En cuanto a los par&#225;metros histol&#243;gicos&#44; la TCG se describi&#243; en el 19&#37; de los pacientes en cualquier momento de la enfermedad y&#44; de estos&#44; el 43&#37; de los casos fueron al diagn&#243;stico&#46; La presencia de TCG en el momento del diagn&#243;stico demostr&#243; un efecto adverso significativo en la supervivencia de estos pacientes &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>C&#41;&#46; La presencia de FT &#40;27&#37; de los casos&#41; no se asoci&#243; a una peor supervivencia sobre toda la cohorte&#44; pero cuando se analiz&#243; sobre la poblaci&#243;n que empez&#243; en estadios iniciales &#60;<span class="elsevierStyleHsp" style=""></span>IIB&#44; se objetiv&#243; que los pacientes con FT presentaban una supervivencia significativamente inferior a los pacientes sin FT &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>D&#41;&#46; Por el contrario&#44; el an&#225;lisis sobre la poblaci&#243;n con estadios &#62;<span class="elsevierStyleHsp" style=""></span>IIB mostr&#243; que la poblaci&#243;n sin FT era la que presentaba una peor supervivencia&#46; La tinci&#243;n intensa de Ki-67 que se encontr&#243; en un 28&#37; de los 108 casos estudiados&#44; tambi&#233;n se asociaba a peor supervivencia&#44; con una media de 85&#44;2 meses y una probabilidad de supervivencia a los 5 a&#241;os del 50&#44;6&#37; en contraste con el grupo que present&#243; un Ki-67 leve&#44; que fue del 92&#44;4&#37; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#59; mientras que en la expresi&#243;n de CD30 no se encontr&#243; dicha asociaci&#243;n&#46; El fenotipo predominante de la serie fue CD4&#43; &#40;83&#37; de los casos&#41; y los casos CD8&#43; y doble negativo CD-&#47;CD8- supon&#237;an el 13&#37; y el 5&#37;&#44; respectivamente&#46; No se encontraron diferencias entre los diferentes fenotipos&#46; Respecto al estudio de clonalidad&#44; la clonalidad en piel que se document&#243; en el 80&#37; de los casos estudiados no se asoci&#243; a una evoluci&#243;n desfavorable&#44; mientras que los pacientes que presentaban clonalidad positiva en sangre &#40;el 39&#37; de los casos&#41; mostraron una peor DSS que los pacientes sin clona &#40;88&#44;7 vs&#46; 143&#44;6 meses&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En relaci&#243;n con los datos anal&#237;ticos&#44; la elevaci&#243;n de LDH &#40;22&#37;&#41; y B2M &#40;30&#37;&#41; tambi&#233;n se asociaron a una peor supervivencia de la cohorte &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">En el an&#225;lisis multivariante&#44; la TCG al diagn&#243;stico &#40;Hazard Ratio &#91;HR&#93; 10&#44;41&#41; y el estadio IVA &#40;HR 6&#44;29&#41; fueron las variables que mostraron un efecto significativo independiente sobre la DSS &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discusi&#243;n</span><p id="par0060" class="elsevierStylePara elsevierViewall">Durante a&#241;os se han intentado dilucidar aquellos factores o marcadores de mal pron&#243;stico que se asocien a una elevada mortalidad&#44; a baja supervivencia o a mayor riesgo de progresi&#243;n de los linfomas<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">6&#44;7</span></a>&#46; En 2013&#44; se propuso el CLIPI <span class="elsevierStyleItalic">&#40;Cutaneous Lymphoma International Prognostic Index&#41;</span>&#44; el primer &#237;ndice pron&#243;stico para linfoma cut&#225;neo&#44; que inclu&#237;a como factores asociados a peor pron&#243;stico en los estadios iniciales &#40;sexo masculino&#44; edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; placas&#44; FT&#44; N1&#47;X&#41; y para estadios avanzados &#40;sexo masculino&#44; edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; estadios B1&#47;B2&#44; N2&#47;N3&#44; afectaci&#243;n visceral&#41; y en funci&#243;n de la puntuaci&#243;n se atribu&#237;a un bajo&#44; intermedio o alto riesgo<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a>&#46; En 2015&#44; el CLIC <span class="elsevierStyleItalic">&#40;Cutaneous Lymphoma International Consortium&#41;</span> emprendi&#243; un proyecto a gran escala denominado ProCLIPI <span class="elsevierStyleItalic">&#40;Prospective Cutaneous Lymphoma International Prognostic Index&#41;</span> dise&#241;ado para crear una base de datos internacional para LCCT con el objetivo a largo plazo de desarrollar un &#237;ndice pron&#243;stico para identificar aquellos pacientes con evoluci&#243;n desfavorable<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">9&#44;10</span></a>&#46; Se han publicado ya algunos estudios prospectivos&#44; como el de Scarisbrick et al&#46; que inclu&#237;a casos avanzados de MF&#47;SS&#44; desarrollando un modelo de &#237;ndice pron&#243;stico con las variables estadio IV&#44; edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; TCG y LDH aumentada<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a>&#46; La gran mayor&#237;a de estos factores&#44; as&#237; como estos &#237;ndices pron&#243;sticos&#44; no han sido validados en la pr&#225;ctica cl&#237;nica y hasta el momento el estadio &#40;TNM&#41; ha sido el marcador pron&#243;stico de m&#225;s valor predictivo<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">4&#44;11</span></a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Este estudio pretende evaluar qu&#233; factores se asocian a un peor pron&#243;stico y un mayor riesgo de progresi&#243;n en una serie de 148 pacientes con MF&#47;SS de un centro de referencia para linfoma cut&#225;neo&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">La edad avanzada &#40;&#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#41; ya se hab&#237;a asociado previamente con un peor pron&#243;stico&#44; especialmente en estadios avanzados<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3&#44;6&#44;12</span></a>&#46; Sin embargo&#44; en esta cohorte no se pudieron evaluar otros factores&#44; como comorbilidades y opciones de tratamiento limitadas&#46; A pesar de que hubo un predominio de pacientes masculinos en el estudio&#44; no se encontraron diferencias significativas en la supervivencia entre sexos&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">El diagn&#243;stico de SS se asoci&#243; con un peor curso de la enfermedad en comparaci&#243;n con la MF&#46; Sin embargo&#44; no se encontraron diferencias en cuanto a DSS entre la MF avanzada y el SS&#44; lo cual sugiere que el estadio al inicio impacta m&#225;s en el pron&#243;stico que el tipo de diagn&#243;stico&#46; En concordancia con estos datos&#44; en la <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>B se muestra que al comparar estadios iniciales con estadio IIB y IVA se observaron diferencias estad&#237;sticamente significativas en la supervivencia&#46; Dichas diferencias se asemejan a los datos previamente publicados donde se observan claras disimilitudes entre la mediana OS de estadios iniciales &#40;IA-IIA&#41; y estadios m&#225;s avanzados &#40;&#62;IIB&#41;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">1&#44;3</span></a>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Entre los pacientes con eritrodermia&#44; no se objetivaron diferencias en la supervivencia de los pacientes con afectaci&#243;n sangu&#237;nea de bajo nivel &#40;IIIB&#41; frente a aquellos sin &#40;IIIA&#41;&#46; En cambio&#44; de acuerdo con los datos previamente publicados<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3&#44;6&#44;13</span></a>&#44; los pacientes con afectaci&#243;n B2 &#40;IVA&#41; mostraron un peor pron&#243;stico &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; en contraste con aquellos con B0 o B1&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Adem&#225;s&#44; no se evidenciaron diferencias en la supervivencia entre pacientes sin afectaci&#243;n ganglionar&#44; aquellos con afectaci&#243;n N1 y N2&#44; pero los pacientes con desaparici&#243;n parcial o total de la arquitectura ganglionar &#40;N3&#41; mostraron una peor evoluci&#243;n&#46; Tambi&#233;n se observ&#243; que los casos con ganglios patol&#243;gicos sin estadificaci&#243;n &#40;Nx&#41; ten&#237;an un mayor riesgo de mortalidad&#44; similar al riesgo de N3&#44; confirmando datos recientemente publicados donde el aumento del tama&#241;o de los ganglios linf&#225;ticos s&#243;lo mediante evaluaci&#243;n cl&#237;nica &#40;Nx&#41; se asoci&#243; con un mayor riesgo de progresi&#243;n<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a>&#59; destacando as&#237; la importancia de realizar biopsias de ganglios palpables para una correcta estadificaci&#243;n&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">La presencia de TCG en el diagn&#243;stico result&#243; ser un marcador histol&#243;gico independiente de mal pron&#243;stico&#44; con una supervivencia a&#250;n peor que la reportada en otros estudios<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3&#44;6&#44;13&#44;14</span></a>&#46; Adem&#225;s&#44; como previamente se hab&#237;a descrito<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">15</span></a>&#44; se observ&#243; que la TCG estaba m&#225;s presente en estadios avanzados&#44; predominando entre los pacientes con estadio IIIB y&#44; espec&#237;ficamente&#44; entre aquellos que pose&#237;an afectaci&#243;n cut&#225;nea en forma de tumor&#46; El fen&#243;meno de FT no mostr&#243; diferencias significativas en la supervivencia en la cohorte estudiada&#44; pero su efecto parece variar seg&#250;n el estadio de la enfermedad&#44; en concordancia con datos previamente publicados donde se objetiv&#243; que el FT actuaba como factor predictor de mala evoluci&#243;n en estadios tempranos<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8&#44;16</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Los valores de Ki-67 y CD30 tambi&#233;n se evaluaron&#44; y Ki-67 intenso se asoci&#243; con un peor pron&#243;stico&#44; mientras que CD30 no mostr&#243; un efecto significativo&#46; Contrariamente&#44; Scarisbrick et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a> objetivaron que la positividad de CD30 se asociaba a peor DSS en aquellos pacientes en fase tumoral T3&#44; estrechamente relacionada con la TCG&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">La clonalidad de las c&#233;lulas T en piel no mostr&#243; efecto pron&#243;stico en la supervivencia&#44; sin embargo&#44; s&#237; se asoci&#243; a un peor pron&#243;stico cuando se objetivaba TCR clonal en sangre &#40;mediana de supervivencia 68 meses&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; De modo similar&#44; Scarisbrick et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a> observaron en su cohorte de MF&#47;SS avanzada un 49&#37; de coincidencia de clonas y una tendencia hacia una peor supervivencia en pacientes con clona sangu&#237;nea &#40;49&#44;8 meses&#41;&#44; pero sin llegar a ser significativa&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Los niveles elevados de LDH y B2M se asociaron con un peor pron&#243;stico en toda la cohorte&#46; En la MF&#44; varios estudios han objetivado que los niveles de LDH se asocian con un mal pron&#243;stico en estadios avanzados<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">6&#44;13&#44;17&#44;18</span></a>&#59; sin embargo&#44; el valor predictivo en estadios iniciales no es claro<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a>&#46; En nuestra cohorte&#44; no se encontraron diferencias significativas en la supervivencia entre los fenotipos CD4&#43;&#44; CD8&#43; o doble negativos&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusiones</span><p id="par0110" class="elsevierStylePara elsevierViewall">En resumen&#44; en este estudio se revisaron 148 casos diagnosticados de MF&#47;SS y se observ&#243; que la edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; el diagn&#243;stico de SS&#44; la presencia de TCG al diagn&#243;stico&#44; el FT en estadios iniciales&#44; un Ki-67 intenso&#44; la presencia de TCR clonal en sangre&#44; una LDH y B2M elevadas&#44; y los estadios IIB&#44; IVA&#44; T3&#44; T4 y N3&#47;Nx fueron factores asociados a un peor pron&#243;stico de la enfermedad&#46; El estadio IVA y la presencia histol&#243;gica de TCG de inicio representaron los dos factores predictivos independientes de pron&#243;stico adverso para la MF&#47;SS&#46; Asimismo&#44; la TCG fue la variable que produjo una disminuci&#243;n m&#225;s acentuada de la supervivencia de los pacientes y estaba estrechamente relacionada con la afectaci&#243;n cut&#225;nea tumoral y el estadio IIB&#46; Sin embargo&#44; se necesitan m&#225;s investigaciones para comprender mejor el impacto de estos factores en la supervivencia de estos pacientes&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Limitaciones</span><p id="par0115" class="elsevierStylePara elsevierViewall">Se trata de un estudio retrospectivo realizado en un solo centro&#44; los resultados pueden carecer de generalizaci&#243;n y no ser aplicables a otras poblaciones o regiones geogr&#225;ficas debido a posibles diferencias en la demograf&#237;a y la atenci&#243;n m&#233;dica&#46; Adem&#225;s&#44; la MF y el SS son patolog&#237;as poco prevalentes&#44; lo que dificulta la obtenci&#243;n de una muestra representativa y podr&#237;a influir en la representatividad de los resultados&#46; La falta de consideraci&#243;n de la variabilidad en los reg&#237;menes de tratamiento es otra limitaci&#243;n significativa&#44; ya que estos tratamientos pueden afectar la progresi&#243;n de la enfermedad y la supervivencia de los pacientes&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicto de intereses</span><p id="par0120" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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          "titulo" => "Keywords"
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          "titulo" => "Introducci&#243;n"
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            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "An&#225;lisis estad&#237;stico"
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        6 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Resultados"
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          "titulo" => "Discusi&#243;n"
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          "identificador" => "sec0030"
          "titulo" => "Conclusiones"
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            0 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Limitaciones"
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          "identificador" => "sec0040"
          "titulo" => "Conflicto de intereses"
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        10 => array:1 [
          "titulo" => "Bibliograf&#237;a"
        ]
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    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2023-10-17"
    "fechaAceptado" => "2023-12-04"
    "PalabrasClave" => array:2 [
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1868487"
          "palabras" => array:6 [
            0 => "Linfomas cut&#225;neos de c&#233;lulas T"
            1 => "Micosis fungoide"
            2 => "S&#237;ndrome S&#233;zary"
            3 => "Transformaci&#243;n a c&#233;lula grande"
            4 => "Supervivencia espec&#237;fica de la enfermedad"
            5 => "Factores pron&#243;sticos"
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      ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1868486"
          "palabras" => array:6 [
            0 => "Cutaneous T-cell lymphomas"
            1 => "Mycosis fungoides"
            2 => "S&#233;zary syndrome"
            3 => "Large cell transformation"
            4 => "Disease-specific survival"
            5 => "Prognostic factors"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Antecedentes y objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Los linfomas cut&#225;neos de c&#233;lulas T &#40;LCCT&#41; como la micosis fungoide &#40;MF&#41; y el s&#237;ndrome de S&#233;zary &#40;SS&#41; son linfomas poco comunes con pron&#243;sticos variables&#46; El objetivo del estudio fue describir la supervivencia de una cohorte de pacientes con MF&#47;SS y evaluar aquellos factores pron&#243;sticos con impacto en la supervivencia de la enfermedad&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se analizaron retrospectivamente todos los casos diagnosticados de MF&#47;SS entre 2008 y 2022&#46; Se evaluaron variables demogr&#225;ficas&#44; par&#225;metros histol&#243;gicos&#44; y datos anal&#237;ticos&#46; Se calcularon la supervivencia libre de progresi&#243;n &#40;PFS&#41; y la supervivencia espec&#237;fica de la enfermedad &#40;DSS&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron un total de 148 casos&#46; Ciento veinti&#250;n casos &#40;82&#37;&#41; fueron diagnosticados de MF y 27 casos de SS&#46; Treinta y siete pacientes &#40;25&#37;&#41; progresaron en alg&#250;n momento de la evoluci&#243;n&#46; La mediana de PFS fue de 127 meses y la mediana de DSS de 135 meses&#46; La edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; el diagn&#243;stico de SS&#44; la presencia de transformaci&#243;n a c&#233;lula grande &#40;TCG&#41; al diagn&#243;stico&#44; el foliculotropismo en estadios iniciales&#44; la elevaci&#243;n de Ki-67&#44; la presencia de TCR clonal en sangre&#44; niveles elevados de LDH y B2M&#44; y estadios avanzados &#40;IIB&#44; IVA&#44; T3&#44; T4&#44; N3&#47;Nx&#41; se asociaron con un peor pron&#243;stico en la cohorte&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El estadio IVA y la presencia de TCG al diagn&#243;stico destacaron como factores independientes de pron&#243;stico desfavorable&#46; La TCG fue la variable que produjo una disminuci&#243;n m&#225;s acentuada de la supervivencia de los pacientes estando estrechamente relacionada con la afectaci&#243;n cut&#225;nea tumoral y el estadio IIB&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Antecedentes y objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusiones"
          ]
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Background and Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Cutaneous T-cell lymphomas &#40;CTCL&#41; such as mycosis fungoides &#40;MF&#41; and S&#233;zary syndrome &#40;SS&#41; are rare lymphomas with varying prognoses&#46; The aim of the study was to describe the survival of a cohort of patients with MF&#47;SS and evaluate the prognostic factors impacting disease survival&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materials and Methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">All cases of MF&#47;SS diagnosed from 2008 through 2022 were retrospectively analyzed&#46; The demographic variables&#44; histological parameters&#44; and analytical data were analyzed too&#46; Progression-free survival &#40;PFS&#41; and disease-specific survival &#40;DSS&#41; were calculated&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A total of 148 cases were included&#46; A total of 121 &#40;82&#37;&#41; and 27 cases were diagnosed with MF&#44; and SS&#44; respectively&#46; A total of 37 patients &#40;25&#37;&#41; experienced progression at some point disease progression&#46; The median PFS and median DSS were 127 and 135 months&#44; respectively&#46; Age &#62;<span class="elsevierStyleHsp" style=""></span>60 years&#44; diagnosis of SS&#44; the presence of large cell transformation &#40;LCT&#41; at diagnosis&#44; folliculotropism in early stages&#44; high Ki-67 expression&#44; the presence of the clonal T-cell receptor &#40;TCR&#41; in blood&#44; elevated LDH and B2M levels&#44; and advanced stages &#40;IIB&#44; IVA&#44; T3&#44; T4&#44; N3&#47;Nx&#41; were associated with worse prognosis across the entire cohort&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Stage IVA and the presence of LCT at diagnosis stood out as independent factors of unfavorable prognosis&#46; LCT was the variable that most significantly impacted the patients&#8217; survival and was closely associated with tumor skin involvement and stage IIB&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0025"
            "titulo" => "Background and Objective"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Materials and Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusions"
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      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 3311
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            "Tamanyo" => 570612
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        "descripcion" => array:1 [
          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Curvas y tablas de supervivencia espec&#237;fica de enfermedad &#40;<span class="elsevierStyleItalic">disease-specific survival</span> &#91;DSS&#93;&#41; de la cohorte de pacientes con MF&#47;SS en las que se compara&#58;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">A&#41; La DSS entre los pacientes con micosis fungoide &#40;MF&#41; y los pacientes con s&#237;ndrome de S&#233;zary &#40;SS&#41;&#46; B&#41; La DSS entre estadios&#46; C&#41; La DSS entre pacientes con transformaci&#243;n a c&#233;lula grande &#40;TCG&#41; al diagn&#243;stico y los que no la presentaban&#46; D&#41; La DSS para la variable foliculotropismo &#40;FT&#41; entre los pacientes con un estadio menor de IIB&#46;</p>"
        ]
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      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabla 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
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            "rol" => "short"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">B2M&#58; beta-2-microglobulina&#59; Dx&#58; diagn&#243;stico&#59; FT&#58; foliculotropismo&#59; LDH&#58; lactato deshidrogenasa&#59; MF&#58; micosis fungoide&#59; SS&#58; s&#237;ndrome de S&#233;zary&#59; TCG&#58; transformaci&#243;n c&#233;lula grande&#59; TCRc&#58; receptor de c&#233;lulas T clonal&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">S&#237;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&nbsp;\t\t\t\t\t\t\n
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Original
Análisis de supervivencia y factores pronósticos en una serie de 148 casos de linfomas cutáneos de células T
Survival Analysis and Prognostic Factors in a Case Series of 148 Cutaneous T-Cell Lymphomas
C. Moreno-Vílcheza, O. Servitjea, Ó. Íñiguez-Arroyob, C. Muniesaa,
Corresponding author
cristinamuniesa@hotmail.com

Autor para correspondencia.
a Servicio de Dermatología, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, España
b Facultad de Medicina y Ciencias de la Salud, Campus Bellvitge, Universitat de Barcelona, Barcelona, España
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">La micosis fungoide &#40;MF&#41; y el s&#237;ndrome de S&#233;zary &#40;SS&#41; son los subtipos m&#225;s frecuentes de linfomas cut&#225;neos de c&#233;lulas T &#40;LCCT&#41;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">1&#44;2</span></a>&#46; La MF suele tener un curso indolente con supervivencias prolongadas y una buena respuesta cl&#237;nica a terapias dirigidas a la piel&#44; sin embargo&#44; alrededor del 20-25&#37; de los pacientes progresan a formas tumorales avanzadas<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a>&#46; Estas formas avanzadas de MF&#44; as&#237; como el SS&#44; son enfermedades agresivas de dif&#237;cil tratamiento y pron&#243;stico adverso<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">1&#44;2</span></a>&#46; Se desconoce todav&#237;a qu&#233; factores est&#225;n implicados en esta progresi&#243;n y en la supervivencia de estos linfomas&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">En este estudio se describe la supervivencia libre de progresi&#243;n &#40;<span class="elsevierStyleItalic">progression-free survival</span> &#91;PFS&#93;&#41; y la supervivencia espec&#237;fica de enfermedad &#40;<span class="elsevierStyleItalic">disease-specific survival</span> &#91;DSS&#93;&#41; de una cohorte de pacientes con MF&#47;SS y se pretende evaluar qu&#233; factores pron&#243;sticos tienen un impacto adverso en la supervivencia de estos linfomas&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material y m&#233;todos</span><p id="par0015" class="elsevierStylePara elsevierViewall">Se analizaron todos los casos consecutivos diagnosticados de MF y SS desde enero de 2008 hasta diciembre de 2022 en la Unidad de Linfoma Cut&#225;neo del Hospital Universitari de Bellvitge&#46; El diagn&#243;stico se hizo seg&#250;n los criterios de la <span class="elsevierStyleItalic">World Health Organization</span> &#40;WHO&#41;-<span class="elsevierStyleItalic">European Organization of Research and Treatment of Cancer</span> &#40;EORTC&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">2</span></a>&#46; Se recogieron datos demogr&#225;ficos &#40;edad&#44; sexo&#44; subtipo diagn&#243;stico&#44; estado &#250;ltimo control&#41;&#44; estadio al diagn&#243;stico y a la progresi&#243;n &#40;la estadificaci&#243;n TNMB se realiz&#243; de acuerdo con el propuesto por la <span class="elsevierStyleItalic">International Society for Cutaneous Lymphoma</span> &#91;ISLC&#93; &#8211; EORTC&#41;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">4</span></a>&#44; par&#225;metros histol&#243;gicos &#40;transformaci&#243;n a c&#233;lula grande &#91;TCG&#93;&#44; foliculotropismo &#91;FT&#93;&#44; porcentaje de c&#233;lulas CD30&#43;&#44; Ki-67&#44; receptor de c&#233;lulas T &#91;TCR&#93; clonal en piel&#41; y par&#225;metros hematol&#243;gicos &#40;LDH&#44; beta2-microglobulina &#91;B2M&#93;&#44; leucocitos&#44; linfocitos&#44; TCR clonal en sangre&#41;&#46; La tinci&#243;n Ki-67 se consider&#243; intensa en aquellas biopsias que expresaron un &#237;ndice de proliferaci&#243;n Ki-67 mayor del 30&#37; y leve en aquellas en las que fue menor del 30&#37;&#46; En cuanto a la LDH y la B2M&#44; se consideraron elevadas si los valores eran mayores de 213<span class="elsevierStyleHsp" style=""></span>U&#47;L y 2&#44;4<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; respectivamente&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Se consider&#243; TCG cuando la presencia de linfocitos grandes exced&#237;a m&#225;s del 25&#37; del infiltrado d&#233;rmico o por la formaci&#243;n de n&#243;dulos de c&#233;lulas grandes<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">La PFS se defini&#243; como el tiempo desde la primera respuesta objetiva al tratamiento hasta la recidiva&#44; progresi&#243;n o fallecimiento &#40;en los pacientes que progresan&#41; o hasta la fecha del &#250;ltimo control &#40;en los pacientes sin progresi&#243;n&#41;&#59; la supervivencia global &#40;<span class="elsevierStyleItalic">overall survival</span> &#91;OS&#93;&#41;&#44; desde la fecha de inicio del tratamiento hasta la fecha de fallecimiento por cualquier causa&#59; y la DSS&#44; desde la fecha del inicio del tratamiento hasta la fecha de fallecimiento a consecuencia del linfoma&#46; Se defini&#243; progresi&#243;n como el cambio de un estadio a otro superior&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lisis estad&#237;stico</span><p id="par0030" class="elsevierStylePara elsevierViewall">Se utilizaron an&#225;lisis y gr&#225;ficos con el software SPSS Statistics para el an&#225;lisis estad&#237;stico&#46; Se realiz&#243; un an&#225;lisis descriptivo de frecuencias para variables categ&#243;ricas y se evalu&#243; la normalidad de las variables num&#233;ricas&#46; Se emplearon tablas de contingencia y pruebas estad&#237;sticas para analizar relaciones entre variables&#46; Se aplic&#243; la prueba de Fisher o la prueba de Ji-Cuadrado seg&#250;n correspondiera&#44; dependiendo del tama&#241;o de las frecuencias esperadas&#46; Se realizaron an&#225;lisis U de Mann-Whitney para comparar variables num&#233;ricas con categ&#243;ricas&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Se estim&#243; la DSS y tasas de supervivencia a diferentes a&#241;os utilizando el m&#233;todo de Kaplan-Meier&#46; Se aplic&#243; la prueba de Log-Rank para comparar grupos&#46; Se llevaron a cabo an&#225;lisis multivariantes utilizando el modelo de regresi&#243;n de riesgos proporcionales de Cox&#44; incluyendo variables significativas de an&#225;lisis previos&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><p id="par0040" class="elsevierStylePara elsevierViewall">Se incluyeron un total de 148 casos&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se describen las caracter&#237;sticas principales de los pacientes con MF y SS&#46; La mediada de edad fue de 62 a&#241;os &#91;49-70 a&#241;os&#93;&#44; con un 63&#37; de hombres&#46; Ciento veinti&#250;n casos &#40;82&#37;&#41; fueron diagnosticados de MF y 27 casos de SS&#46; Al diagn&#243;stico&#44; los estadios iniciales &#40; <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se incluye tambi&#233;n los resultados del an&#225;lisis univariante Kaplan-Meier&#47;Log-Rank de supervivencia espec&#237;fica de la cohorte para cada una de las variables que a continuaci&#243;n se detallan&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">En el an&#225;lisis univariante&#44; la edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os &#40;52&#37; de los casos&#41; se asoci&#243; a una peor DSS con una media de supervivencia de 121 meses&#46; 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y IVA2 en el caso de pacientes con afectaci&#243;n ganglionar N3 &#40;mediana DSS 14 meses&#41;&#44; no se encontraron diferencias entre ambos grupos&#46; Sin embargo&#44; al comparar la supervivencia de N3 y&#47;o Nx &#40;ganglios perif&#233;ricos an&#243;malos sin confirmaci&#243;n histol&#243;gica&#41; con la de N1 y&#47;o N2 s&#237; se evidenciaron diferencias&#46; Tambi&#233;n se encontraron diferencias en la supervivencia entre los pacientes con afectaci&#243;n B2 &#40;IVA&#41;&#44; que mostraron un peor pron&#243;stico &#40;62&#44;6 vs&#46; 146&#44;5 meses&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; que aquellos con B0 o B1&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">En cuanto a los par&#225;metros histol&#243;gicos&#44; la TCG se describi&#243; en el 19&#37; de los pacientes en cualquier momento de la enfermedad y&#44; de estos&#44; el 43&#37; de los casos fueron al diagn&#243;stico&#46; La presencia de TCG en el momento del diagn&#243;stico demostr&#243; un efecto adverso significativo en la supervivencia de estos pacientes &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>C&#41;&#46; La presencia de FT &#40;27&#37; de los casos&#41; no se asoci&#243; a una peor supervivencia sobre toda la cohorte&#44; pero cuando se analiz&#243; sobre la poblaci&#243;n que empez&#243; en estadios iniciales &#60;<span class="elsevierStyleHsp" style=""></span>IIB&#44; se objetiv&#243; que los pacientes con FT presentaban una supervivencia significativamente inferior a los pacientes sin FT &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>D&#41;&#46; Por el contrario&#44; el an&#225;lisis sobre la poblaci&#243;n con estadios &#62;<span class="elsevierStyleHsp" style=""></span>IIB mostr&#243; que la poblaci&#243;n sin FT era la que presentaba una peor supervivencia&#46; La tinci&#243;n intensa de Ki-67 que se encontr&#243; en un 28&#37; de los 108 casos estudiados&#44; tambi&#233;n se asociaba a peor supervivencia&#44; con una media de 85&#44;2 meses y una probabilidad de supervivencia a los 5 a&#241;os del 50&#44;6&#37; en contraste con el grupo que present&#243; un Ki-67 leve&#44; que fue del 92&#44;4&#37; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#59; mientras que en la expresi&#243;n de CD30 no se encontr&#243; dicha asociaci&#243;n&#46; El fenotipo predominante de la serie fue CD4&#43; &#40;83&#37; de los casos&#41; y los casos CD8&#43; y doble negativo CD-&#47;CD8- supon&#237;an el 13&#37; y el 5&#37;&#44; respectivamente&#46; No se encontraron diferencias entre los diferentes fenotipos&#46; Respecto al estudio de clonalidad&#44; la clonalidad en piel que se document&#243; en el 80&#37; de los casos estudiados no se asoci&#243; a una evoluci&#243;n desfavorable&#44; mientras que los pacientes que presentaban clonalidad positiva en sangre &#40;el 39&#37; de los casos&#41; mostraron una peor DSS que los pacientes sin clona &#40;88&#44;7 vs&#46; 143&#44;6 meses&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En relaci&#243;n con los datos anal&#237;ticos&#44; la elevaci&#243;n de LDH &#40;22&#37;&#41; y B2M &#40;30&#37;&#41; tambi&#233;n se asociaron a una peor supervivencia de la cohorte &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">En el an&#225;lisis multivariante&#44; la TCG al diagn&#243;stico &#40;Hazard Ratio &#91;HR&#93; 10&#44;41&#41; y el estadio IVA &#40;HR 6&#44;29&#41; fueron las variables que mostraron un efecto significativo independiente sobre la DSS &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discusi&#243;n</span><p id="par0060" class="elsevierStylePara elsevierViewall">Durante a&#241;os se han intentado dilucidar aquellos factores o marcadores de mal pron&#243;stico que se asocien a una elevada mortalidad&#44; a baja supervivencia o a mayor riesgo de progresi&#243;n de los linfomas<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">6&#44;7</span></a>&#46; En 2013&#44; se propuso el CLIPI <span class="elsevierStyleItalic">&#40;Cutaneous Lymphoma International Prognostic Index&#41;</span>&#44; el primer &#237;ndice pron&#243;stico para linfoma cut&#225;neo&#44; que inclu&#237;a como factores asociados a peor pron&#243;stico en los estadios iniciales &#40;sexo masculino&#44; edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; placas&#44; FT&#44; N1&#47;X&#41; y para estadios avanzados &#40;sexo masculino&#44; edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; estadios B1&#47;B2&#44; N2&#47;N3&#44; afectaci&#243;n visceral&#41; y en funci&#243;n de la puntuaci&#243;n se atribu&#237;a un bajo&#44; intermedio o alto riesgo<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a>&#46; En 2015&#44; el CLIC <span class="elsevierStyleItalic">&#40;Cutaneous Lymphoma International Consortium&#41;</span> emprendi&#243; un proyecto a gran escala denominado ProCLIPI <span class="elsevierStyleItalic">&#40;Prospective Cutaneous Lymphoma International Prognostic Index&#41;</span> dise&#241;ado para crear una base de datos internacional para LCCT con el objetivo a largo plazo de desarrollar un &#237;ndice pron&#243;stico para identificar aquellos pacientes con evoluci&#243;n desfavorable<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">9&#44;10</span></a>&#46; Se han publicado ya algunos estudios prospectivos&#44; como el de Scarisbrick et al&#46; que inclu&#237;a casos avanzados de MF&#47;SS&#44; desarrollando un modelo de &#237;ndice pron&#243;stico con las variables estadio IV&#44; edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; TCG y LDH aumentada<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a>&#46; La gran mayor&#237;a de estos factores&#44; as&#237; como estos &#237;ndices pron&#243;sticos&#44; no han sido validados en la pr&#225;ctica cl&#237;nica y hasta el momento el estadio &#40;TNM&#41; ha sido el marcador pron&#243;stico de m&#225;s valor predictivo<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">4&#44;11</span></a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Este estudio pretende evaluar qu&#233; factores se asocian a un peor pron&#243;stico y un mayor riesgo de progresi&#243;n en una serie de 148 pacientes con MF&#47;SS de un centro de referencia para linfoma cut&#225;neo&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">La edad avanzada &#40;&#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#41; ya se hab&#237;a asociado previamente con un peor pron&#243;stico&#44; especialmente en estadios avanzados<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3&#44;6&#44;12</span></a>&#46; Sin embargo&#44; en esta cohorte no se pudieron evaluar otros factores&#44; como comorbilidades y opciones de tratamiento limitadas&#46; A pesar de que hubo un predominio de pacientes masculinos en el estudio&#44; no se encontraron diferencias significativas en la supervivencia entre sexos&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">El diagn&#243;stico de SS se asoci&#243; con un peor curso de la enfermedad en comparaci&#243;n con la MF&#46; Sin embargo&#44; no se encontraron diferencias en cuanto a DSS entre la MF avanzada y el SS&#44; lo cual sugiere que el estadio al inicio impacta m&#225;s en el pron&#243;stico que el tipo de diagn&#243;stico&#46; En concordancia con estos datos&#44; en la <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>B se muestra que al comparar estadios iniciales con estadio IIB y IVA se observaron diferencias estad&#237;sticamente significativas en la supervivencia&#46; Dichas diferencias se asemejan a los datos previamente publicados donde se observan claras disimilitudes entre la mediana OS de estadios iniciales &#40;IA-IIA&#41; y estadios m&#225;s avanzados &#40;&#62;IIB&#41;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">1&#44;3</span></a>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Entre los pacientes con eritrodermia&#44; no se objetivaron diferencias en la supervivencia de los pacientes con afectaci&#243;n sangu&#237;nea de bajo nivel &#40;IIIB&#41; frente a aquellos sin &#40;IIIA&#41;&#46; En cambio&#44; de acuerdo con los datos previamente publicados<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3&#44;6&#44;13</span></a>&#44; los pacientes con afectaci&#243;n B2 &#40;IVA&#41; mostraron un peor pron&#243;stico &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; en contraste con aquellos con B0 o B1&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Adem&#225;s&#44; no se evidenciaron diferencias en la supervivencia entre pacientes sin afectaci&#243;n ganglionar&#44; aquellos con afectaci&#243;n N1 y N2&#44; pero los pacientes con desaparici&#243;n parcial o total de la arquitectura ganglionar &#40;N3&#41; mostraron una peor evoluci&#243;n&#46; Tambi&#233;n se observ&#243; que los casos con ganglios patol&#243;gicos sin estadificaci&#243;n &#40;Nx&#41; ten&#237;an un mayor riesgo de mortalidad&#44; similar al riesgo de N3&#44; confirmando datos recientemente publicados donde el aumento del tama&#241;o de los ganglios linf&#225;ticos s&#243;lo mediante evaluaci&#243;n cl&#237;nica &#40;Nx&#41; se asoci&#243; con un mayor riesgo de progresi&#243;n<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a>&#59; destacando as&#237; la importancia de realizar biopsias de ganglios palpables para una correcta estadificaci&#243;n&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">La presencia de TCG en el diagn&#243;stico result&#243; ser un marcador histol&#243;gico independiente de mal pron&#243;stico&#44; con una supervivencia a&#250;n peor que la reportada en otros estudios<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3&#44;6&#44;13&#44;14</span></a>&#46; Adem&#225;s&#44; como previamente se hab&#237;a descrito<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">15</span></a>&#44; se observ&#243; que la TCG estaba m&#225;s presente en estadios avanzados&#44; predominando entre los pacientes con estadio IIIB y&#44; espec&#237;ficamente&#44; entre aquellos que pose&#237;an afectaci&#243;n cut&#225;nea en forma de tumor&#46; El fen&#243;meno de FT no mostr&#243; diferencias significativas en la supervivencia en la cohorte estudiada&#44; pero su efecto parece variar seg&#250;n el estadio de la enfermedad&#44; en concordancia con datos previamente publicados donde se objetiv&#243; que el FT actuaba como factor predictor de mala evoluci&#243;n en estadios tempranos<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8&#44;16</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Los valores de Ki-67 y CD30 tambi&#233;n se evaluaron&#44; y Ki-67 intenso se asoci&#243; con un peor pron&#243;stico&#44; mientras que CD30 no mostr&#243; un efecto significativo&#46; Contrariamente&#44; Scarisbrick et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a> objetivaron que la positividad de CD30 se asociaba a peor DSS en aquellos pacientes en fase tumoral T3&#44; estrechamente relacionada con la TCG&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">La clonalidad de las c&#233;lulas T en piel no mostr&#243; efecto pron&#243;stico en la supervivencia&#44; sin embargo&#44; s&#237; se asoci&#243; a un peor pron&#243;stico cuando se objetivaba TCR clonal en sangre &#40;mediana de supervivencia 68 meses&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; De modo similar&#44; Scarisbrick et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a> observaron en su cohorte de MF&#47;SS avanzada un 49&#37; de coincidencia de clonas y una tendencia hacia una peor supervivencia en pacientes con clona sangu&#237;nea &#40;49&#44;8 meses&#41;&#44; pero sin llegar a ser significativa&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Los niveles elevados de LDH y B2M se asociaron con un peor pron&#243;stico en toda la cohorte&#46; En la MF&#44; varios estudios han objetivado que los niveles de LDH se asocian con un mal pron&#243;stico en estadios avanzados<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">6&#44;13&#44;17&#44;18</span></a>&#59; sin embargo&#44; el valor predictivo en estadios iniciales no es claro<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a>&#46; En nuestra cohorte&#44; no se encontraron diferencias significativas en la supervivencia entre los fenotipos CD4&#43;&#44; CD8&#43; o doble negativos&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusiones</span><p id="par0110" class="elsevierStylePara elsevierViewall">En resumen&#44; en este estudio se revisaron 148 casos diagnosticados de MF&#47;SS y se observ&#243; que la edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; el diagn&#243;stico de SS&#44; la presencia de TCG al diagn&#243;stico&#44; el FT en estadios iniciales&#44; un Ki-67 intenso&#44; la presencia de TCR clonal en sangre&#44; una LDH y B2M elevadas&#44; y los estadios IIB&#44; IVA&#44; T3&#44; T4 y N3&#47;Nx fueron factores asociados a un peor pron&#243;stico de la enfermedad&#46; El estadio IVA y la presencia histol&#243;gica de TCG de inicio representaron los dos factores predictivos independientes de pron&#243;stico adverso para la MF&#47;SS&#46; Asimismo&#44; la TCG fue la variable que produjo una disminuci&#243;n m&#225;s acentuada de la supervivencia de los pacientes y estaba estrechamente relacionada con la afectaci&#243;n cut&#225;nea tumoral y el estadio IIB&#46; Sin embargo&#44; se necesitan m&#225;s investigaciones para comprender mejor el impacto de estos factores en la supervivencia de estos pacientes&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Limitaciones</span><p id="par0115" class="elsevierStylePara elsevierViewall">Se trata de un estudio retrospectivo realizado en un solo centro&#44; los resultados pueden carecer de generalizaci&#243;n y no ser aplicables a otras poblaciones o regiones geogr&#225;ficas debido a posibles diferencias en la demograf&#237;a y la atenci&#243;n m&#233;dica&#46; Adem&#225;s&#44; la MF y el SS son patolog&#237;as poco prevalentes&#44; lo que dificulta la obtenci&#243;n de una muestra representativa y podr&#237;a influir en la representatividad de los resultados&#46; La falta de consideraci&#243;n de la variabilidad en los reg&#237;menes de tratamiento es otra limitaci&#243;n significativa&#44; ya que estos tratamientos pueden afectar la progresi&#243;n de la enfermedad y la supervivencia de los pacientes&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicto de intereses</span><p id="par0120" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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            0 => "Linfomas cut&#225;neos de c&#233;lulas T"
            1 => "Micosis fungoide"
            2 => "S&#237;ndrome S&#233;zary"
            3 => "Transformaci&#243;n a c&#233;lula grande"
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            0 => "Cutaneous T-cell lymphomas"
            1 => "Mycosis fungoides"
            2 => "S&#233;zary syndrome"
            3 => "Large cell transformation"
            4 => "Disease-specific survival"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Antecedentes y objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Los linfomas cut&#225;neos de c&#233;lulas T &#40;LCCT&#41; como la micosis fungoide &#40;MF&#41; y el s&#237;ndrome de S&#233;zary &#40;SS&#41; son linfomas poco comunes con pron&#243;sticos variables&#46; El objetivo del estudio fue describir la supervivencia de una cohorte de pacientes con MF&#47;SS y evaluar aquellos factores pron&#243;sticos con impacto en la supervivencia de la enfermedad&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se analizaron retrospectivamente todos los casos diagnosticados de MF&#47;SS entre 2008 y 2022&#46; Se evaluaron variables demogr&#225;ficas&#44; par&#225;metros histol&#243;gicos&#44; y datos anal&#237;ticos&#46; Se calcularon la supervivencia libre de progresi&#243;n &#40;PFS&#41; y la supervivencia espec&#237;fica de la enfermedad &#40;DSS&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron un total de 148 casos&#46; Ciento veinti&#250;n casos &#40;82&#37;&#41; fueron diagnosticados de MF y 27 casos de SS&#46; Treinta y siete pacientes &#40;25&#37;&#41; progresaron en alg&#250;n momento de la evoluci&#243;n&#46; La mediana de PFS fue de 127 meses y la mediana de DSS de 135 meses&#46; La edad &#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; el diagn&#243;stico de SS&#44; la presencia de transformaci&#243;n a c&#233;lula grande &#40;TCG&#41; al diagn&#243;stico&#44; el foliculotropismo en estadios iniciales&#44; la elevaci&#243;n de Ki-67&#44; la presencia de TCR clonal en sangre&#44; niveles elevados de LDH y B2M&#44; y estadios avanzados &#40;IIB&#44; IVA&#44; T3&#44; T4&#44; N3&#47;Nx&#41; se asociaron con un peor pron&#243;stico en la cohorte&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El estadio IVA y la presencia de TCG al diagn&#243;stico destacaron como factores independientes de pron&#243;stico desfavorable&#46; La TCG fue la variable que produjo una disminuci&#243;n m&#225;s acentuada de la supervivencia de los pacientes estando estrechamente relacionada con la afectaci&#243;n cut&#225;nea tumoral y el estadio IIB&#46;</p></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Background and Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Cutaneous T-cell lymphomas &#40;CTCL&#41; such as mycosis fungoides &#40;MF&#41; and S&#233;zary syndrome &#40;SS&#41; are rare lymphomas with varying prognoses&#46; The aim of the study was to describe the survival of a cohort of patients with MF&#47;SS and evaluate the prognostic factors impacting disease survival&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materials and Methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">All cases of MF&#47;SS diagnosed from 2008 through 2022 were retrospectively analyzed&#46; The demographic variables&#44; histological parameters&#44; and analytical data were analyzed too&#46; Progression-free survival &#40;PFS&#41; and disease-specific survival &#40;DSS&#41; were calculated&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A total of 148 cases were included&#46; A total of 121 &#40;82&#37;&#41; and 27 cases were diagnosed with MF&#44; and SS&#44; respectively&#46; A total of 37 patients &#40;25&#37;&#41; experienced progression at some point disease progression&#46; The median PFS and median DSS were 127 and 135 months&#44; respectively&#46; Age &#62;<span class="elsevierStyleHsp" style=""></span>60 years&#44; diagnosis of SS&#44; the presence of large cell transformation &#40;LCT&#41; at diagnosis&#44; folliculotropism in early stages&#44; high Ki-67 expression&#44; the presence of the clonal T-cell receptor &#40;TCR&#41; in blood&#44; elevated LDH and B2M levels&#44; and advanced stages &#40;IIB&#44; IVA&#44; T3&#44; T4&#44; N3&#47;Nx&#41; were associated with worse prognosis across the entire cohort&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Stage IVA and the presence of LCT at diagnosis stood out as independent factors of unfavorable prognosis&#46; LCT was the variable that most significantly impacted the patients&#8217; survival and was closely associated with tumor skin involvement and stage IIB&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Background and Objective"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Materials and Methods"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusions"
          ]
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    "multimedia" => array:2 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 3311
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        "descripcion" => array:1 [
          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Curvas y tablas de supervivencia espec&#237;fica de enfermedad &#40;<span class="elsevierStyleItalic">disease-specific survival</span> &#91;DSS&#93;&#41; de la cohorte de pacientes con MF&#47;SS en las que se compara&#58;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">A&#41; La DSS entre los pacientes con micosis fungoide &#40;MF&#41; y los pacientes con s&#237;ndrome de S&#233;zary &#40;SS&#41;&#46; B&#41; La DSS entre estadios&#46; C&#41; La DSS entre pacientes con transformaci&#243;n a c&#233;lula grande &#40;TCG&#41; al diagn&#243;stico y los que no la presentaban&#46; D&#41; La DSS para la variable foliculotropismo &#40;FT&#41; entre los pacientes con un estadio menor de IIB&#46;</p>"
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      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabla 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
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            "identificador" => "at1"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">B2M&#58; beta-2-microglobulina&#59; Dx&#58; diagn&#243;stico&#59; FT&#58; foliculotropismo&#59; LDH&#58; lactato deshidrogenasa&#59; MF&#58; micosis fungoide&#59; SS&#58; s&#237;ndrome de S&#233;zary&#59; TCG&#58; transformaci&#243;n c&#233;lula grande&#59; TCRc&#58; receptor de c&#233;lulas T clonal&#46;</p>"
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ISSN: 00017310
Original language: Spanish
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