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diagnosed with stage IVA<span class="elsevierStyleInf">1</span> SS &#40;T4&#44; N0&#44; M0&#44; B2&#41; who were treated with alemtuzumab between 2008 and 2012&#46; Four patients had undergone previous treatments &#40;phototherapy&#44; prednisone&#44; methotrexate&#44; gemcitabine&#44; and bexarotene&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Data were gathered on the following variables to assess the treatment with alemtuzumab &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#58; duration&#44; type of response&#44; time until onset of the response&#44; duration of the response after the interruption of treatment&#44; and peripheral blood S&#233;zary cells&#46; In addition&#44; we analyzed the clinical course&#44; follow-up period&#44; and complications associated with alemtuzumab&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The type of response was classified as follows&#58; complete response &#40;CR&#41;&#44; partial response &#40;PR&#41;&#44; or disease progression &#40;DP&#41;&#44; in accordance with the study by Olsen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The regimen used was the subcutaneous administration of an initial dose of 3<span class="elsevierStyleHsp" style=""></span>mg&#44; followed by doses of 10<span class="elsevierStyleHsp" style=""></span>mg 3 times per week&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The 5 patients received oral prophylaxis with sulfamethoxazole-trimethoprim&#44; aciclovir&#44; and fluconazole for <span class="elsevierStyleItalic">Pneumocystis jiroveci</span>&#44; herpesvirus&#44; and <span class="elsevierStyleItalic">Candida</span>&#46; For cytomegalovirus &#40;CMV&#41; prophylaxis&#44; we performed weekly measurement of the viral load and administered anticipatory treatment with oral valganciclovir in the event of reactivation&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">A response was achieved in 4 of the 5 patients &#40;overall response rate&#44; 80&#37;&#41;&#59; there were 2 PR &#40;40&#37;&#41; and 2 CR &#40;40&#37;&#41;&#46; The median duration of treatment was 8 weeks &#40;range&#44; 4-13 weeks&#41; and the median duration of the response after the interruption of treatment was 13 months &#40;range&#44; 5-66 months&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Complications included pneumococcal pneumonia in 1 patient&#44; a cytokine release syndrome in 3&#44; and subclinical CMV reactivation in 2&#46; There were no hematological complications&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The median follow-up was 27 months &#40;range&#44; 23-67 months&#41; after the initiation of treatment&#46; One patient died at 24 months due to transformation to a high-grade nonHodgkin lymphoma&#46; At the time of writing&#44; 3 patients are in progression and one continues in complete remission 67 months after completing the treatment&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">Alemtuzumab has been used in both refractory&#44; advanced-stage MF and in SS&#46; The first description is from 1998 in 8 patients with MF&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a> In 2003&#44; the usefulness of alemtuzumab was demonstrated in a phase <span class="elsevierStyleSmallCaps">ii</span> study of 22 patients with MF or SS&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> A number of small series and case reports have been published since that time&#46; In the literature reviewed&#44; we found a total of 13 series<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">4&#44;6&#8211;17</span></a> &#40;detailed in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41; and 6 case reports of MF and SS&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The overall responses to treatment in the 2 largest studies&#8212;of 22 and 39 patients&#8212;were 55&#37; and 51&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">8&#44;9</span></a> The median duration of the response was 12 months&#44; although this varied between series&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">4&#44;6&#8211;17</span></a> In the series of 39 cases&#44; lasting remissions &#40;more than 2 years&#41; were observed in 5 patients with SS but in only 1 patient with MF&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">9</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The treatment regimen has changed over the years&#46; The drug was administered intravenously in the initial studies&#58; sequential initial doses of 3<span class="elsevierStyleHsp" style=""></span>mg&#44; 10<span class="elsevierStyleHsp" style=""></span>mg&#44; and 30<span class="elsevierStyleHsp" style=""></span>mg were administered&#44; followed by 30<span class="elsevierStyleHsp" style=""></span>mg 3 times a week&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">7&#44;8&#44;10&#8211;13</span></a> It was subsequently observed that alemtuzumab could be equally effective administered subcutaneously at low doses&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">4&#44;14</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Treatment-related complications include infection and hematologic toxicity&#46; The regimen of 10<span class="elsevierStyleHsp" style=""></span>mg subcutaneously has been shown to be associated with a lower incidence of these side effects&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">4&#44;14&#44;15</span></a> The most common opportunistic infection is CMV reactivation&#44; although other types of infection have also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> Myelosuppression is the most common hematologic toxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Cytokine release syndrome is the most common complication during treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">7&#44;8&#44;10&#44;11</span></a> Its frequency can be reduced by progressive dose escalation&#46; Lenihan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> published 4 cases of cardiac toxicity during the treatment of previously healthy patients&#46; As this has not been observed in any other study&#44; the possibility of a causal relationship remains under debate&#46; A case of cutaneous hemophagocytosis at the site of injection of alemtuzumab was recently reported in a patient without Epstein-Barr virus reactivation&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">In the literature reviewed&#44; alemtuzumab has been used indistinctly for MF and for SS&#44; and advanced-stage SS and MF are grouped together in most studies&#46; Erythrodermic MF is now considered to be progression of MF with absent or minimal blood involvement&#44; in contrast to the situation with SS&#44; which arises de novo and shows significant blood involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> In 2012&#44; Clark et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">6</span></a> reported that alemtuzumab may only be effective when blood involvement is present &#40;in SS and in cases of erythrodermic MF with blood involvement&#41;&#46; Those authors suggested that the 2 diseases arose from distinct types of memory T cells&#58; the malignant lymphocytes in patients with SS have a CCR7&#43;&#47;L-selectin&#43; central memory cell phenotype &#40;migratory cells that are found in peripheral blood&#44; in the skin&#44; and in lymph nodes&#41;&#44; whereas the malignant lymphocytes of MF arise from nonmigratory cells resident in the skin and that are not found in the peripheral blood&#46; Alemtuzumab depletes all T lymphocytes in the blood&#44; but the population of cells resident in the skin will escape from the effect of the antibody and persist after treatment&#46; In addition&#44; alemtuzumab requires the presence of neutrophils and natural killer cells &#40;both of which are present in blood but not in skin&#41; to achieve lymphocyte depletion&#44; and hence it only eliminates cells in the peripheral blood&#46; The main candidates for this treatment are therefore patients with SS&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Unfortunately&#44; authorization for the indication of this drug in B-cell chronic lymphocytic leukemic and other hematological diseases was withdrawn in August 2012&#44; and it is currently only available for multiple sclerosis&#46; For the treatment of patients with SS&#44; alemtuzumab can only be obtained by individualized access via protocol&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0100" class="elsevierStylePara elsevierViewall">We have presented 5 cases of SS treated with alemtuzumab&#44; achieving an 80&#37; response rate&#46; The regimen of 10<span class="elsevierStyleHsp" style=""></span>mg administered subcutaneously was well tolerated and the median duration of the response was 13 months&#46; Alemtuzumab can be a useful drug in cases of SS refractory to other treatments&#44; achieving a rapid clinical response and improvement in quality of life&#44; with a reduction or remission of the pruritus&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflicts of Interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Ethical Disclosures</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Protection of human and animal subjects</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this research&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Confidentiality of data</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data are disclosed in this article&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Right to privacy and informed consent</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data are disclosed in this article&#46;</p></span></span></span>"
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    "fechaRecibido" => "2014-09-24"
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            2 => "Treatment"
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            0 => "S&#237;ndrome de S&#233;zary"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Alemtuzumab is a monoclonal antibody that has been used to treat refractory cases of S&#233;zary syndrome &#40;SS&#41; and advanced mycosis fungoides&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We present 5 patients with SS who were treated with alemtuzumab between 2008 and 2012&#44; with an overall response rate of 80&#37; &#40;40&#37; partial response and 40&#37; complete response&#41;&#46; A regimen of 10<span class="elsevierStyleHsp" style=""></span>mg administered subcutaneously was well tolerated with acceptable toxicity&#46; The median duration of response was 13 months&#46; However&#44; one patient remains in complete remission after 67 months&#44; a remarkable outcome given the low survival rate associated with SS&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In conclusion&#44; we believe that alemtuzumab may be useful in cases of SS refractory to other treatments&#46; As there are no curative treatments for SS&#44; alemtuzumab should be considered as a therapeutic option&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El alemtuzumab es un anticuerpo monoclonal que se ha utilizado como terap&#233;utica en casos refractarios de s&#237;ndrome de S&#233;zary &#40;SS&#41; y micosis fungoide en estadio avanzado&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Presentamos 5 pacientes diagnosticados de SS tratados con alemtuzumab entre los a&#241;os 2008 y 2012&#44; con una tasa de respuesta global del 80&#37; &#40;40&#37; respuestas parciales y 40&#37; respuestas completas&#41;&#46; La pauta de 10<span class="elsevierStyleHsp" style=""></span>mg v&#237;a subcut&#225;nea fue bien tolerada y con una toxicidad aceptable&#46; En nuestra casu&#237;stica la mediana de duraci&#243;n de la respuesta fue de 13 meses&#44; sin embargo uno de los pacientes contin&#250;a en remisi&#243;n completa tras 67 meses&#44; hecho destacable dada la baja supervivencia del SS&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Como conclusi&#243;n&#44; creemos que el alemtuzumab es un f&#225;rmaco que podr&#237;a ser &#250;til en casos de SS refractarios a otros tratamientos&#46; Dado que no existen tratamientos curativos en el SS&#44; ser&#237;a una alternativa terap&#233;utica a tener en cuenta&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; del Alc&#225;zar-Viladomiu E&#44; Tuneu-Valls A&#44; L&#243;pez-Pesta&#241;a A&#44; Vidal-Mance&#241;ido MJ&#46; Tratamiento del s&#237;ndrome de S&#233;zary con alemtuzumab&#58; serie de 5 casos y revisi&#243;n de la literatura&#46; Actas Dermosifiliogr&#46; 2015&#59;106&#58;e33&#8211;e39&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A&#44; Erythematous lesions on the abdomen of a patient with SS before starting treatment with alemtuzumab &#40;case<span class="elsevierStyleHsp" style=""></span>3&#41;&#46; B&#44; In the same patient&#44; resolution of the erythema 4 weeks after starting treatment with alemtuzumab&#46;</p>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; LN&#44; lymph node&#59; NCI&#44; National Cancer Institute&#59; TCR&#44; T-cell receptor&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Olsen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a></p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Skin &#40;T&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Limited patches&#44; papules&#44; and&#47;or plaques covering &#60;<span class="elsevierStyleHsp" style=""></span>10&#37; of the skin surface&#46; T<span class="elsevierStyleInf">1a</span> &#40;patches only&#41; and T<span class="elsevierStyleInf">1b</span> &#40;patches and plaques&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patches&#44; papules&#44; and&#47;or plaques covering &#8805;<span class="elsevierStyleHsp" style=""></span>10&#37; of the skin surface&#46; T<span class="elsevierStyleInf">2a</span> &#40;patches only&#41; and T<span class="elsevierStyleInf">2b</span> &#40;patches and plaques&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">One or more tumors &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>cm in diameter&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Confluent erythema covering<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>80&#37; of the skin surface&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Nodes &#40;N&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No abnormal peripheral lymph nodes&#46; Biopsy not required&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinically abnormal peripheral lymph nodes&#59; histologically Dutch grade 1 or NCI LN<span class="elsevierStyleInf">0-2</span>&#46; N<span class="elsevierStyleInf">1a</span>&#44; clone negative&#59; N<span class="elsevierStyleInf">1b</span>&#44; clone positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinically abnormal peripheral lymph nodes&#59; histologically Dutch grade 2 or NCI LN<span class="elsevierStyleInf">3</span>&#46; N<span class="elsevierStyleInf">2a</span>&#44; clone negative&#59; N<span class="elsevierStyleInf">2b</span>&#44; clone positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinically abnormal peripheral lymph nodes&#44; histologically Dutch grade 3-4 or NCI LN<span class="elsevierStyleInf">4</span>&#59; clone positive or negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinically abnormal lymph nodes without histological confirmation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Visceral &#40;M&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No visceral involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Visceral involvement &#40;histological confirmation required and organ must be specified&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Blood &#40;B&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>B0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Absence of significant blood involvement &#40;&#8804;<span class="elsevierStyleHsp" style=""></span>5&#37; atypical lymphocytes &#91;S&#233;zary cells&#93;&#41;&#46; B<span class="elsevierStyleInf">0a</span>&#44; clone negative&#59; B<span class="elsevierStyleInf">0b</span>&#44; clone positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>B1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Low blood tumor burden &#40;&#62;<span class="elsevierStyleHsp" style=""></span>5&#37; atypical lymphocytes &#91;S&#233;zary cells&#93;&#41;&#46; B<span class="elsevierStyleInf">1a</span>&#44; clone negative&#59; B<span class="elsevierStyleInf">1b</span>&#44; clone positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>B2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High blood tumor burden defined as one of the following&#58; &#8805;<span class="elsevierStyleHsp" style=""></span>1&#44;000 S&#233;zary cells&#47;&#956;L with positive TCR&#59; CD4&#47;CD8<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10 with positive TCR&#59; or CD4&#43; CD7- cells <span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>40&#37; or CD4&#43; CD26- cells &#8805;<span class="elsevierStyleHsp" style=""></span>30&#37; with positive TCR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Classification of Mycosis Fungoides&#47;S&#233;zary Syndrome Proposed by the International Society for Cutaneous Lymphomas and the European Organisation for Research and Treatment of Cancer&#46;</p>"
        ]
      ]
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        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; IFN&#44; interferon&#59; HSCT&#44; hematopoietic stem cell transplant&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Source&#58; modified from Jawed et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a></p>"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type of therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Immune modulators</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Interferon &#40;IFN alfa and IFN gamma&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Retinoid &#40;bexarotene&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Denileukin diftitox&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Extracorporeal photophoresis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Biologics</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Alemtuzumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Radiotherapy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Total body irradiation with electrons <span class="elsevierStyleItalic">&#40;electron beam&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Combine treatments</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFN alfa<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>phototherapy or retinoid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Retinoid<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>phototherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Extracorporeal photophoresis<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IFN alfa or retinoid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Systemic chemotherapy</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Monotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Methotrexate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pegylated doxorubicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Polychemotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Purine&#47;pyrimidine analogues &#40;fludarabine&#44; 2-chlorodeoxyadenosine&#44; deoxycoformycin&#44; gemcitabine&#44; forodesine&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Alkylating agents &#40;chlorambucil&#44; nitrogen mustard&#44; cyclophosphamide&#44; temozolomide&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topoisomerase inhibitors &#40;etoposide&#44; pegylated doxorubicin&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histone deacetylase inhibitors &#40;vorinostat&#44; romidepsin&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHOP and CHOP-like&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>HSCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Autologous&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Allogeneic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Nonmyeloablative allogeneic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Treatments Used in S&#233;zary Syndrome&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; CR&#44; complete response&#59; DP&#44; disease progression&#59; F&#58; female&#59; M&#44; male&#59; NHL&#44; non-Hodgkin lymphoma&#59; PR&#44; partial response&#59; X&#175;&#44; median values&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TreatmentDuration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Time to ResponseOnset&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type of Cutaneous Response<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type of Blood Response&#44;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>S&#233;zary Cells&#47;&#956;L and &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Overall Response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Duration of the response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Complications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical Course and Follow-up After Starting Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">F&#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CRPre&#8594;1050 &#40;7&#37;&#41;Post&#8594;0 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">66<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CR67<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">M&#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CRPre&#8594;9530 &#40;32&#37;&#41;Post&#8594;147 &#40;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cytokine release syndromeCMV reactivationPneumococcal pneumonia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Death due to high-grade NHL24<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">F&#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PRPre&#8594;1215 &#40;12&#37;&#41;Post&#8594;379 &#40;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Retreatment at 4<span class="elsevierStyleHsp" style=""></span>wk with no improvement&#46;Currently chlorambucil-prednisone27<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">M&#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CRPre&#8594;554 &#40;4&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>Post&#8594;0 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cytokine release syndromeCMV reactivation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Currently photophoresis32<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">F&#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CRPre&#8594;1342 &#40;8&#37;&#41;Post&#8594;55 &#40;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not recorded&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cytokine release syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Allogeneic bone marrow transplant20<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">X&#175;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab873625.png"
              ]
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          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">CR&#58; 100&#37; lesion clearance&#59; PR&#58; 50&#37;-99&#37; clearance of initial lesions with no new tumors &#40;T3&#41; in patients with T1&#44; T2&#44; or T4&#59; DP&#58;<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>25&#37; increase in skin disease or new tumors &#40;T3&#41; in patients with T1&#44; T2&#44; or T4&#44; or loss of response in patients with complete response or partial response&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a></p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">CR&#58; B<span class="elsevierStyleInf">0</span> and PR<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>50&#37; reduction in the initial blood tumor burden&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a></p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Patient 4 presented &#60;<span class="elsevierStyleHsp" style=""></span>1000 Sez&#225;ry cells but a CD4&#47;CD8 ratio<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10 and was therefore considered to have stage IVA<span class="elsevierStyleInf">1</span> disease&#44; as the others&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Our Series of 5 Patients With S&#233;zary Syndrome Treated With Alemtuzumab&#46;</p>"
        ]
      ]
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        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AMI&#44; acute myocardial infarction&#59; CBCL&#44; cutaneous B-cell lymphoma&#59; CHF&#44; congestive heart failure&#59; CMV&#44; cytomegalovirus&#59; CR&#44; complete response&#59; CTCL&#44; cutaneous T-cell lymphoma&#59; CTCL-L&#44; leukemic cutaneous T-cell lymphoma&#59; DP&#44; disease progression&#59; EBV&#44; Epstein Barr virus&#59; FUO&#44; fever of unknown origin&#59; HSV&#44; herpes simplex virus&#59; MRSA&#44; methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#59; NHL&#44; non-Hodgkin lymphoma&#59; OR&#44; overall response&#59; PR&#44; partial response&#59; SC&#44; subcutaneous&#59; SD&#44; stable disease&#59; TB&#44; tuberculosis&#59; TCL&#44; T-cell lymphoma&#59; VZV&#44; varicella-zoster virus&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No&#46;&#176; of Patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Alemtuzumab Regimen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment Duration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical Response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Response Duration &#40;Median&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Serious Complications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Lundin J et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a> &#40;1998&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50 low grade NHL&#40;8<span class="elsevierStyleHsp" style=""></span>MF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30<span class="elsevierStyleHsp" style=""></span>mg IV on 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6-12<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OR<span class="elsevierStyleHsp" style=""></span>20&#37;MF&#58; CR<span class="elsevierStyleHsp" style=""></span>50&#37;&#44; 2<span class="elsevierStyleHsp" style=""></span>CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Opportunistic infections &#40;7&#41;&#44; sepsis &#40;9&#41;&#44; grade <span class="elsevierStyleSmallCaps">iv</span> neutropenia &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Lundin J et al&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> &#40;2003&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22<span class="elsevierStyleHsp" style=""></span>MF&#47;SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30<span class="elsevierStyleHsp" style=""></span>mg IV on 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CR<span class="elsevierStyleHsp" style=""></span>55&#37;7<span class="elsevierStyleHsp" style=""></span>CR&#44; 5<span class="elsevierStyleHsp" style=""></span>PR&#44; 3<span class="elsevierStyleHsp" style=""></span>SD&#44; 7<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CMV reactivation &#40;4&#41;&#44; FUO &#40;3&#41;&#44; generalized HSV &#40;1&#41;&#44; pulmonary aspergillosis &#40;1&#41;&#44; <span class="elsevierStyleItalic">Mycobacterium pneumoniae</span> &#40;1&#41;&#44; febrile neutropenia &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Kennedy GA et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">10</span></a> &#40;2003&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>MF&#47;2<span class="elsevierStyleHsp" style=""></span>SS1<span class="elsevierStyleHsp" style=""></span>MF transformed to large cell&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30<span class="elsevierStyleHsp" style=""></span>mg IV on 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3-13<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OR<span class="elsevierStyleHsp" style=""></span>38&#37;3<span class="elsevierStyleHsp" style=""></span>PR&#44; 2<span class="elsevierStyleHsp" style=""></span>SD&#44; 3<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Less than 3<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Grade <span class="elsevierStyleSmallCaps">iv</span> pancytopenia with sepsis &#40;2&#41;&#44; cutaneous MRSA and oral HSV &#40;1&#41;&#44; viral bronchiolitis &#40;1&#41;&#44; cutaneous VZV &#40;1&#41;&#44; CMV &#40;1&#41;&#44; <span class="elsevierStyleItalic">Pseudomonas</span> osteomyelitis and Parvovirus infection &#40;1&#41;&#44; sepsis due to <span class="elsevierStyleItalic">Klebsiella</span> &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Ferrajoli et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a> &#40;2003&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6<span class="elsevierStyleHsp" style=""></span>CTCL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30<span class="elsevierStyleHsp" style=""></span>mg IV on 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4-12<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Capalbo S et al&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a> &#40;2003&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>MF&#47;2<span class="elsevierStyleHsp" style=""></span>SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30<span class="elsevierStyleHsp" style=""></span>mg IV on 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#44; 6&#44; and 12<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>CR&#44; 1<span class="elsevierStyleHsp" style=""></span>PR&#44; 1 death &#40;AMI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11<span class="elsevierStyleHsp" style=""></span>mo3<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Lenihan DJ et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> &#40;2004&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>SS and 3<span class="elsevierStyleHsp" style=""></span>MF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30<span class="elsevierStyleHsp" style=""></span>mg IV on 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;5<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3<span class="elsevierStyleHsp" style=""></span>PR&#44; 2<span class="elsevierStyleHsp" style=""></span>SD&#44; 3<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cardiovascular events &#40;5&#41;&#58; CHF&#47;arrhythmiaTwo deaths from unspecified infectionsOne <span class="elsevierStyleItalic">Legionella pneumoniae</span> pneumonia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Zinzani et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a> &#40;2005&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>MF6<span class="elsevierStyleHsp" style=""></span>peripheral TCL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mg SC 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3<span class="elsevierStyleHsp" style=""></span>PR &#40;MF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CMV reactivation &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bernengo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> &#40;2007&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14<span class="elsevierStyleHsp" style=""></span>SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10-15<span class="elsevierStyleHsp" style=""></span>mg SC 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>CR&#44; 11<span class="elsevierStyleHsp" style=""></span>PR&#44; 2<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Infections in patients treated with 15<span class="elsevierStyleHsp" style=""></span>mg&#58;Staphylococcal sepsis &#40;1&#41;Subclinical CMV reactivation &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Alinari et al&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">15</span></a> &#40;2007&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30<span class="elsevierStyleHsp" style=""></span>mg SC 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5-9<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OR<span class="elsevierStyleHsp" style=""></span>100&#37;5<span class="elsevierStyleHsp" style=""></span>CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asymptomatic CMV reactivation &#40;2&#41;&#44; EBV reactivation &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Querfeld et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a> &#40;2009&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17<span class="elsevierStyleHsp" style=""></span>SS2<span class="elsevierStyleHsp" style=""></span>erythrodermic MF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30<span class="elsevierStyleHsp" style=""></span>mg IV and SC 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OR<span class="elsevierStyleHsp" style=""></span>84&#37;9<span class="elsevierStyleHsp" style=""></span>CR&#44; 7<span class="elsevierStyleHsp" style=""></span>PR&#44; 3<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Death due to grade <span class="elsevierStyleSmallCaps">iv</span> pancytopenia &#40;1&#41;Cervical abscess &#40;1&#41;&#44; MRSA sepsis &#40;1&#41;&#44; herpes zoster &#40;1&#41;&#44; central venous catheter infection &#40;1&#41;&#44; febrile neutropenia &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Clark level et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">6</span></a> &#40;2012&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18<span class="elsevierStyleHsp" style=""></span>CTCL-L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mg SC 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OR<span class="elsevierStyleHsp" style=""></span>89&#37;9<span class="elsevierStyleHsp" style=""></span>CR&#44; 7<span class="elsevierStyleHsp" style=""></span>PR&#44; 2<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CMV reactivation &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">De Masson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">9</span></a> &#40;2014&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23<span class="elsevierStyleHsp" style=""></span>SS&#47;16<span class="elsevierStyleHsp" style=""></span>MF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30<span class="elsevierStyleHsp" style=""></span>mg IV and SC 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OR<span class="elsevierStyleHsp" style=""></span>51&#37;&#40;70&#37; SS&#44; 25&#37; MF&#41;7<span class="elsevierStyleHsp" style=""></span>CR &#40;6<span class="elsevierStyleHsp" style=""></span>SS&#44; 1<span class="elsevierStyleHsp" style=""></span>MF&#41;13<span class="elsevierStyleHsp" style=""></span>PR &#40;10<span class="elsevierStyleHsp" style=""></span>SS&#44; 3<span class="elsevierStyleHsp" style=""></span>MF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;4<span class="elsevierStyleHsp" style=""></span>mo6 patients <span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>mo&#40;5<span class="elsevierStyleHsp" style=""></span>SS&#44; 1<span class="elsevierStyleHsp" style=""></span>MF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CMV viremia &#40;10&#41;&#44; TB &#40;2&#41;&#44; cutaneous <span class="elsevierStyleItalic">Mycobacterium chelonae</span> infection &#40;1&#41;&#44; bacterial infection &#40;5&#41;&#44; toxoplasmosis &#40;1&#41;&#44; aspergillosis &#40;1&#41;&#44; pneumonia &#40;7&#41;&#44; grade 3 cytopenia &#40;10&#41;&#44; death &#40;2&#41;&#44; transformation to large cell CTCL &#40;5&#41;&#44; large cell CBCL &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Watanabe et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a> &#40;2014&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17<span class="elsevierStyleHsp" style=""></span>SS&#47;6<span class="elsevierStyleHsp" style=""></span>MF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mg SC 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SS&#58; 13<span class="elsevierStyleHsp" style=""></span>CR&#44; 4<span class="elsevierStyleHsp" style=""></span>PRMF&#58; 1<span class="elsevierStyleHsp" style=""></span>CR after electron beam&#44; 5<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Our series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mg SC 3<span class="elsevierStyleHsp" style=""></span>d&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8<span class="elsevierStyleHsp" style=""></span>wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>CR&#44; 2<span class="elsevierStyleHsp" style=""></span>PR&#44; 1<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13<span class="elsevierStyleHsp" style=""></span>mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pneumococcal pneumonia &#40;1&#41;Asymptomatic CMV reactivation &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Published Series of Patients With SS&#47;MF Treated With Alemtuzumab&#46;</p>"
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Vol. 106. Núm. 7.
Páginas e33-e39 (septiembre 2015)
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6077
Vol. 106. Núm. 7.
Páginas e33-e39 (septiembre 2015)
e-Case Report
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Treatment of Sézary Syndrome With Alemtuzumab: A Series of 5 Cases and a Review of the Literature
Tratamiento del síndrome de Sézary con alemtuzumab: serie de 5 casos y revisión de la literatura
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6077
E. del Alcázar-Viladomiua,
Autor para correspondencia
, A. Tuneu-Vallsa, A. López-Pestañaa, M.J. Vidal-Manceñidob
a Servicio de Dermatología, Hospital Universitario Donostia, San Sebastián, Spain
b Servicio de Hematología, Hospital Universitario Donostia, San Sebastián, Spain
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Table 1. Classification of Mycosis Fungoides/Sézary Syndrome Proposed by the International Society for Cutaneous Lymphomas and the European Organisation for Research and Treatment of Cancer.
Table 2. Treatments Used in Sézary Syndrome.
Table 3. Our Series of 5 Patients With Sézary Syndrome Treated With Alemtuzumab.
Table 4. Published Series of Patients With SS/MF Treated With Alemtuzumab.
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Abstract

Alemtuzumab is a monoclonal antibody that has been used to treat refractory cases of Sézary syndrome (SS) and advanced mycosis fungoides.

We present 5 patients with SS who were treated with alemtuzumab between 2008 and 2012, with an overall response rate of 80% (40% partial response and 40% complete response). A regimen of 10mg administered subcutaneously was well tolerated with acceptable toxicity. The median duration of response was 13 months. However, one patient remains in complete remission after 67 months, a remarkable outcome given the low survival rate associated with SS.

In conclusion, we believe that alemtuzumab may be useful in cases of SS refractory to other treatments. As there are no curative treatments for SS, alemtuzumab should be considered as a therapeutic option.

Keywords:
Sézary syndrome
Alemtuzumab
Treatment
Resumen

El alemtuzumab es un anticuerpo monoclonal que se ha utilizado como terapéutica en casos refractarios de síndrome de Sézary (SS) y micosis fungoide en estadio avanzado.

Presentamos 5 pacientes diagnosticados de SS tratados con alemtuzumab entre los años 2008 y 2012, con una tasa de respuesta global del 80% (40% respuestas parciales y 40% respuestas completas). La pauta de 10mg vía subcutánea fue bien tolerada y con una toxicidad aceptable. En nuestra casuística la mediana de duración de la respuesta fue de 13 meses, sin embargo uno de los pacientes continúa en remisión completa tras 67 meses, hecho destacable dada la baja supervivencia del SS.

Como conclusión, creemos que el alemtuzumab es un fármaco que podría ser útil en casos de SS refractarios a otros tratamientos. Dado que no existen tratamientos curativos en el SS, sería una alternativa terapéutica a tener en cuenta.

Palabras clave:
Síndrome de Sézary
Alemtuzumab
Tratamiento
Texto completo
Introduction

Sézary syndrome (SS) is a rare disorder that accounts for approximately 3% of all cutaneous T-cell lymphomas. It is considered to be an aggressive variant characterized by the presence of erythroderma and circulating atypical T cells (Sézary cells), with or without lymphadenopathy.1 SS is classified as T4, N0-3, M0-1, B2 according to the International Society for Cutaneous Lymphomas (Table 1).1–3 Pruritus is the main symptom and can have a marked impact on quality of life.

Table 1.

Classification of Mycosis Fungoides/Sézary Syndrome Proposed by the International Society for Cutaneous Lymphomas and the European Organisation for Research and Treatment of Cancer.

Skin (T)
T1  Limited patches, papules, and/or plaques covering <10% of the skin surface. T1a (patches only) and T1b (patches and plaques) 
T2  Patches, papules, and/or plaques covering ≥10% of the skin surface. T2a (patches only) and T2b (patches and plaques) 
T3  One or more tumors (≥1cm in diameter) 
T4  Confluent erythema covering80% of the skin surface 
Nodes (N)
N0  No abnormal peripheral lymph nodes. Biopsy not required 
N1  Clinically abnormal peripheral lymph nodes; histologically Dutch grade 1 or NCI LN0-2. N1a, clone negative; N1b, clone positive 
N2  Clinically abnormal peripheral lymph nodes; histologically Dutch grade 2 or NCI LN3. N2a, clone negative; N2b, clone positive 
N3  Clinically abnormal peripheral lymph nodes, histologically Dutch grade 3-4 or NCI LN4; clone positive or negative 
Nx  Clinically abnormal lymph nodes without histological confirmation 
Visceral (M)
M0  No visceral involvement 
M1  Visceral involvement (histological confirmation required and organ must be specified) 
Blood (B)
B0  Absence of significant blood involvement (≤5% atypical lymphocytes [Sézary cells]). B0a, clone negative; B0b, clone positive 
B1  Low blood tumor burden (>5% atypical lymphocytes [Sézary cells]). B1a, clone negative; B1b, clone positive 
B2  High blood tumor burden defined as one of the following: ≥1,000 Sézary cells/μL with positive TCR; CD4/CD8>10 with positive TCR; or CD4+ CD7- cells 40% or CD4+ CD26- cells ≥30% with positive TCR 

Abbreviations: LN, lymph node; NCI, National Cancer Institute; TCR, T-cell receptor.

Source: Olsen et al.2

The prognosis is poor, with a 5-year survival of 24%; few lasting responses or remissions have been reported after treatment.4

Systemic therapies are necessary for treatment, as those that exclusively target the skin are insufficient. The therapeutic choice is determined by the spread of the disease, the impact on quality of life, and the patient's age and comorbid conditions. Although several treatments are available for SS (Table 2),3 few efficacy studies have been published.

Table 2.

Treatments Used in Sézary Syndrome.

Type of therapy  Treatment 
Immune modulators  Interferon (IFN alfa and IFN gamma) 
  Retinoid (bexarotene) 
  Denileukin diftitox 
  Extracorporeal photophoresis 
Biologics  Alemtuzumab 
Radiotherapy  Total body irradiation with electrons (electron beam) 
Combine treatments  IFN alfa+phototherapy or retinoid 
  Retinoid+phototherapy 
  Extracorporeal photophoresis+IFN alfa or retinoid 
Systemic chemotherapy
Monotherapy  Methotrexate 
  Pegylated doxorubicin 
Polychemotherapy  Purine/pyrimidine analogues (fludarabine, 2-chlorodeoxyadenosine, deoxycoformycin, gemcitabine, forodesine) 
  Alkylating agents (chlorambucil, nitrogen mustard, cyclophosphamide, temozolomide) 
  Topoisomerase inhibitors (etoposide, pegylated doxorubicin) 
  Histone deacetylase inhibitors (vorinostat, romidepsin) 
  CHOP and CHOP-like 
HSCT  Autologous 
  Allogeneic 
  Nonmyeloablative allogeneic 
   

Abbreviations: IFN, interferon; HSCT, hematopoietic stem cell transplant.

Source: modified from Jawed et al.3

New therapies for SS, including biological therapies, have appeared in recent years. Alemtuzumab is a humanized monoclonal antibody that targets the CD52 glycoprotein expressed on the surface of T and B cells, natural killer cells, monocytes, and macrophages, leading to a depletion of those cells in the peripheral blood.3,5 It is thought to act by direct cell lysis mediated by neutrophils, complement, and antibody-dependent cytotoxicity and apoptosis.3–6 In 2001, alemtuzumab was approved for the treatment of B-cell chronic lymphocytic leukemia, although some authors have used it in cases of refractory SS and advanced mycosis fungoides (MF).

Case Descriptions

We present 5 patients (3 women and 2 men) diagnosed with stage IVA1 SS (T4, N0, M0, B2) who were treated with alemtuzumab between 2008 and 2012. Four patients had undergone previous treatments (phototherapy, prednisone, methotrexate, gemcitabine, and bexarotene).

Data were gathered on the following variables to assess the treatment with alemtuzumab (Table 3): duration, type of response, time until onset of the response, duration of the response after the interruption of treatment, and peripheral blood Sézary cells. In addition, we analyzed the clinical course, follow-up period, and complications associated with alemtuzumab.

Table 3.

Our Series of 5 Patients With Sézary Syndrome Treated With Alemtuzumab.

Sex  Age  TreatmentDuration  Time to ResponseOnset  Type of Cutaneous Responsea  Type of Blood Response,bSézary Cells/μL and %  Overall Response  Duration of the response  Complications  Clinical Course and Follow-up After Starting Treatment 
F(1)  57  4wk  4wk  CR  CRPre→1050 (7%)Post→0 (0%)  CR  66mo  No  CR67mo 
M(2)  65  8wk  2wk  CR  CRPre→9530 (32%)Post→147 (3%)  CR  11mo  Cytokine release syndromeCMV reactivationPneumococcal pneumonia  Death due to high-grade NHL24mo 
F(3)  85  13wk  4wk  CR  PRPre→1215 (12%)Post→379 (6%)  PR  5mo  No  Retreatment at 4wk with no improvement.Currently chlorambucil-prednisone27mo 
M(4)  75  5wk  1wk  PR  CRPre→554 (4%)cPost→0 (0%)  PR  15mo  Cytokine release syndromeCMV reactivation  Currently photophoresis32mo 
F(5)  57  10wk  No response  DP  CRPre→1342 (8%)Post→55 (1%)  DP  Not recorded  Cytokine release syndrome  Allogeneic bone marrow transplant20mo 
X¯  65  8wk  3wk        13mo     

Abbreviations: CR, complete response; DP, disease progression; F: female; M, male; NHL, non-Hodgkin lymphoma; PR, partial response; X¯, median values.

a

CR: 100% lesion clearance; PR: 50%-99% clearance of initial lesions with no new tumors (T3) in patients with T1, T2, or T4; DP:25% increase in skin disease or new tumors (T3) in patients with T1, T2, or T4, or loss of response in patients with complete response or partial response.2

b

CR: B0 and PR>50% reduction in the initial blood tumor burden.2

c

Patient 4 presented <1000 Sezáry cells but a CD4/CD8 ratio>10 and was therefore considered to have stage IVA1 disease, as the others.

The type of response was classified as follows: complete response (CR), partial response (PR), or disease progression (DP), in accordance with the study by Olsen et al.2 (Figure 1).

Figure 1.

A, Erythematous lesions on the abdomen of a patient with SS before starting treatment with alemtuzumab (case3). B, In the same patient, resolution of the erythema 4 weeks after starting treatment with alemtuzumab.

(0.16MB).

The regimen used was the subcutaneous administration of an initial dose of 3mg, followed by doses of 10mg 3 times per week.

The 5 patients received oral prophylaxis with sulfamethoxazole-trimethoprim, aciclovir, and fluconazole for Pneumocystis jiroveci, herpesvirus, and Candida. For cytomegalovirus (CMV) prophylaxis, we performed weekly measurement of the viral load and administered anticipatory treatment with oral valganciclovir in the event of reactivation.

A response was achieved in 4 of the 5 patients (overall response rate, 80%); there were 2 PR (40%) and 2 CR (40%). The median duration of treatment was 8 weeks (range, 4-13 weeks) and the median duration of the response after the interruption of treatment was 13 months (range, 5-66 months).

Complications included pneumococcal pneumonia in 1 patient, a cytokine release syndrome in 3, and subclinical CMV reactivation in 2. There were no hematological complications.

The median follow-up was 27 months (range, 23-67 months) after the initiation of treatment. One patient died at 24 months due to transformation to a high-grade nonHodgkin lymphoma. At the time of writing, 3 patients are in progression and one continues in complete remission 67 months after completing the treatment.

Discussion

Alemtuzumab has been used in both refractory, advanced-stage MF and in SS. The first description is from 1998 in 8 patients with MF.7 In 2003, the usefulness of alemtuzumab was demonstrated in a phase ii study of 22 patients with MF or SS.8 A number of small series and case reports have been published since that time. In the literature reviewed, we found a total of 13 series4,6–17 (detailed in Table 4) and 6 case reports of MF and SS.

Table 4.

Published Series of Patients With SS/MF Treated With Alemtuzumab.

Series  No.° of Patients  Alemtuzumab Regimen  Treatment Duration  Clinical Response  Response Duration (Median)  Serious Complications 
Lundin J et al.7 (1998)  50 low grade NHL(8MF)  30mg IV on 3d/wk  6-12wk  OR20%MF: CR50%, 2CR  10mo  Opportunistic infections (7), sepsis (9), grade iv neutropenia (14) 
Lundin J et al.8 (2003)  22MF/SS  30mg IV on 3d/wk  10wk  CR55%7CR, 5PR, 3SD, 7DP  12mo  CMV reactivation (4), FUO (3), generalized HSV (1), pulmonary aspergillosis (1), Mycobacterium pneumoniae (1), febrile neutropenia (1) 
Kennedy GA et al.10 (2003)  5MF/2SS1MF transformed to large cell  30mg IV on 3d/wk  3-13wk  OR38%3PR, 2SD, 3DP  Less than 3mo  Grade iv pancytopenia with sepsis (2), cutaneous MRSA and oral HSV (1), viral bronchiolitis (1), cutaneous VZV (1), CMV (1), Pseudomonas osteomyelitis and Parvovirus infection (1), sepsis due to Klebsiella (1) 
Ferrajoli et al.,11 (2003)  6CTCL  30mg IV on 3d/wk  4-12wk  2PR  NS  NS 
Capalbo S et al.12 (2003)  1MF/2SS  30mg IV on 3d/wk  3, 6, and 12wk  1CR, 1PR, 1 death (AMI)  11mo3mo  No 
Lenihan DJ et al.13 (2004)  5SS and 3MF  30mg IV on 3d/wk  8.5wk  3PR, 2SD, 3DP  NS  Cardiovascular events (5): CHF/arrhythmiaTwo deaths from unspecified infectionsOne Legionella pneumoniae pneumonia 
Zinzani et al.,14 (2005)  4MF6peripheral TCL  10mg SC 3d/wk  4wk  3PR (MF)  NS  CMV reactivation (1) 
Bernengo et al.4 (2007)  14SS  10-15mg SC 3d/wk  NS  1CR, 11PR, 2SD  12mo  Infections in patients treated with 15mg:Staphylococcal sepsis (1)Subclinical CMV reactivation (3) 
Alinari et al.15 (2007)  5SS  30mg SC 3d/wk  5-9wk  OR100%5CR  8wk  Asymptomatic CMV reactivation (2), EBV reactivation (1) 
Querfeld et al.,16 (2009)  17SS2erythrodermic MF  30mg IV and SC 3d/wk  12wk  OR84%9CR, 7PR, 3DP  6mo  Death due to grade iv pancytopenia (1)Cervical abscess (1), MRSA sepsis (1), herpes zoster (1), central venous catheter infection (1), febrile neutropenia (1) 
Clark level et al.6 (2012)  18CTCL-L  10mg SC 3d/wk  6wk  OR89%9CR, 7PR, 2DP  NS  CMV reactivation (1) 
De Masson et al.9 (2014)  23SS/16MF  30mg IV and SC 3d/wk  12wk  OR51%(70% SS, 25% MF)7CR (6SS, 1MF)13PR (10SS, 3MF)  3.4mo6 patients >24mo(5SS, 1MF)  CMV viremia (10), TB (2), cutaneous Mycobacterium chelonae infection (1), bacterial infection (5), toxoplasmosis (1), aspergillosis (1), pneumonia (7), grade 3 cytopenia (10), death (2), transformation to large cell CTCL (5), large cell CBCL (1) 
Watanabe et al.17 (2014)  17SS/6MF  10mg SC 3d/wk  NS  SS: 13CR, 4PRMF: 1CR after electron beam, 5DP  NS  NS 
Our series  5SS  10mg SC 3d/wk  8wk  2CR, 2PR, 1DP  13mo  Pneumococcal pneumonia (1)Asymptomatic CMV reactivation (2) 

Abbreviations: AMI, acute myocardial infarction; CBCL, cutaneous B-cell lymphoma; CHF, congestive heart failure; CMV, cytomegalovirus; CR, complete response; CTCL, cutaneous T-cell lymphoma; CTCL-L, leukemic cutaneous T-cell lymphoma; DP, disease progression; EBV, Epstein Barr virus; FUO, fever of unknown origin; HSV, herpes simplex virus; MRSA, methicillin-resistant Staphylococcus aureus; NHL, non-Hodgkin lymphoma; OR, overall response; PR, partial response; SC, subcutaneous; SD, stable disease; TB, tuberculosis; TCL, T-cell lymphoma; VZV, varicella-zoster virus.

The overall responses to treatment in the 2 largest studies—of 22 and 39 patients—were 55% and 51%, respectively.8,9 The median duration of the response was 12 months, although this varied between series.4,6–17 In the series of 39 cases, lasting remissions (more than 2 years) were observed in 5 patients with SS but in only 1 patient with MF.9

The treatment regimen has changed over the years. The drug was administered intravenously in the initial studies: sequential initial doses of 3mg, 10mg, and 30mg were administered, followed by 30mg 3 times a week.7,8,10–13 It was subsequently observed that alemtuzumab could be equally effective administered subcutaneously at low doses.4,14

Treatment-related complications include infection and hematologic toxicity. The regimen of 10mg subcutaneously has been shown to be associated with a lower incidence of these side effects.4,14,15 The most common opportunistic infection is CMV reactivation, although other types of infection have also been reported.4 Myelosuppression is the most common hematologic toxicity.4

Cytokine release syndrome is the most common complication during treatment.7,8,10,11 Its frequency can be reduced by progressive dose escalation. Lenihan et al.13 published 4 cases of cardiac toxicity during the treatment of previously healthy patients. As this has not been observed in any other study, the possibility of a causal relationship remains under debate. A case of cutaneous hemophagocytosis at the site of injection of alemtuzumab was recently reported in a patient without Epstein-Barr virus reactivation.18

In the literature reviewed, alemtuzumab has been used indistinctly for MF and for SS, and advanced-stage SS and MF are grouped together in most studies. Erythrodermic MF is now considered to be progression of MF with absent or minimal blood involvement, in contrast to the situation with SS, which arises de novo and shows significant blood involvement.1 In 2012, Clark et al.6 reported that alemtuzumab may only be effective when blood involvement is present (in SS and in cases of erythrodermic MF with blood involvement). Those authors suggested that the 2 diseases arose from distinct types of memory T cells: the malignant lymphocytes in patients with SS have a CCR7+/L-selectin+ central memory cell phenotype (migratory cells that are found in peripheral blood, in the skin, and in lymph nodes), whereas the malignant lymphocytes of MF arise from nonmigratory cells resident in the skin and that are not found in the peripheral blood. Alemtuzumab depletes all T lymphocytes in the blood, but the population of cells resident in the skin will escape from the effect of the antibody and persist after treatment. In addition, alemtuzumab requires the presence of neutrophils and natural killer cells (both of which are present in blood but not in skin) to achieve lymphocyte depletion, and hence it only eliminates cells in the peripheral blood. The main candidates for this treatment are therefore patients with SS.

Unfortunately, authorization for the indication of this drug in B-cell chronic lymphocytic leukemic and other hematological diseases was withdrawn in August 2012, and it is currently only available for multiple sclerosis. For the treatment of patients with SS, alemtuzumab can only be obtained by individualized access via protocol.

Conclusions

We have presented 5 cases of SS treated with alemtuzumab, achieving an 80% response rate. The regimen of 10mg administered subcutaneously was well tolerated and the median duration of the response was 13 months. Alemtuzumab can be a useful drug in cases of SS refractory to other treatments, achieving a rapid clinical response and improvement in quality of life, with a reduction or remission of the pruritus.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Ethical DisclosuresProtection of human and animal subjects

The authors declare that no experiments were performed on humans or animals for this research.

Confidentiality of data

The authors declare that no private patient data are disclosed in this article.

Right to privacy and informed consent

The authors declare that no private patient data are disclosed in this article.

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Please cite this article as: del Alcázar-Viladomiu E, Tuneu-Valls A, López-Pestaña A, Vidal-Manceñido MJ. Tratamiento del síndrome de Sézary con alemtuzumab: serie de 5 casos y revisión de la literatura. Actas Dermosifiliogr. 2015;106:e33–e39.

Copyright © 2014. Elsevier España, S.L.U. and AEDV
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