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Differential diagnosis should include systemic diffuse large cell non-Hodgkin lymphoma &#40;NHL&#41; with cutaneous involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In recent years&#44; systemic rituximab alone or in combination with chemotherapeutic agents has been introduced for the treatment of CDLBCL-LT&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Rituximab</span><p id="par0010" class="elsevierStylePara elsevierViewall">Rituximab is a murine-human chimeric monoclonal immunoglobulin G antibody against the CD20 antigen present on almost all neoplastic and normal B-cells&#46; It has been used successfully in the treatment of systemic B-cell NHL either as monotherapy or more commonly in combination with other chemotherapeutic agents&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In recent years&#44; rituximab has been used by dermatologists with good outcomes in a range of skin diseases<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and CBCLs&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In vitro studies of rituximab have shown this agent induces lysis of lymphoma B-cells by antibody-dependent cell mediated cytotoxicity&#44; complement activation&#44; and direct induction of apoptosis&#46; This mechanism does not depend on the immune system and occurs because the variable region of murine origin binds with high affinity to the CD20 antigen expressed on malignant B lymphocytes&#44; halting their proliferation and inducing apoptosis probably through transmembrane calcium channels&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Rituximab has also been shown to induce an antigen-specific response in T cells by an immunization mechanism&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Additionally the drug is able to sensitize cells to the cytotoxic effects of other chemotherapeutic agents&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Rituximab is also known to act via the bcl-2 protein&#46; This marker is overexpressed in 85&#37; of CDLBCL-LT and is considered one of the factors associated with worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In the case of systemic diffuse large cell lymphomas&#44; the addition of rituximab to combinations based on anthracyclines is particularly beneficial for bcl-2 positive lymphomas&#44; which had a worse prognosis before rituximab was available&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Rituximab in Primary Cutaneous Lymphomas</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Follicular Lymphoma and Marginal Zone Lymphoma</span><p id="par0025" class="elsevierStylePara elsevierViewall">Primary cutaneous FL and MZL are cutaneous lymphomas with an indolent course despite the high rates of recurrence&#46; It is therefore important to highlight that treatment should not be aggressive in most cases&#46; The recommendations for management of LF and MZL include withholding treatment &#40;<span class="elsevierStyleItalic">watchful waiting</span>&#41;&#44; RT&#44; surgery&#44; or intralesional interferon alfa&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Sometimes&#44; however&#44; large&#44; painful&#44; disfiguring&#44; or itchy multiple lesions may be present&#59; watchful waiting is not an option and treatment should be administered&#46; Moreover&#44; in these situations&#44; local skin interventions&#44; such as surgery or RT&#44; are not appropriate&#44; particularly in the case of multiple lesions or lesions on sites such as the face or neck where the interventions might leave substantial esthetic sequelae&#46; In these circumstances&#44; other treatment alternatives&#44; among them systemic or intralesional rituximab&#44; have been used&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a> summarize the published cases of FL and MZL&#44; respectively&#44; treated with systemic rituximab&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> summarizes the cases of FL and MZL treated with intralesional administration of rituximab&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">In total&#44; 44 cases have been published of cutaneous FL treated with intravenous rituximab &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;24</span></a> Regimens have ranged from the usual 4 infusions&#44; once a week&#44; with standard doses of 375<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> to courses of up to 10 infusions&#46; The complete response rate for all the published cases is approximately 77&#37;&#44; with a response duration ranging from 6 to 57 months&#46; For MZL&#44; 16 cases of systemic rituximab treatment have been published &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;18&#44;21&#44;25&#44;26</span></a> with an overall complete response rate of 43&#37; and a duration of response of between 6 and 75 months&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">This apparently worse response to rituximab in patients with MZL is pending confirmation in the future in large prospective studies&#59; if real&#44; the difference could be due to several mechanisms that confer resistance to rituximab&#46; A study has been published describing the lack of efficacy of rituximab in patients with noncutaneous MZL who also received chemoimmunotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> One of the hypotheses is that malignant B cells acquire new mutations that confer resistance to rituximab-induced apoptosis&#46; Thus&#44; in a study of 4 patients with recurrent disease&#44; an increase in bcl-2 activity was observed after rituximab treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Variations in the site of B-cell binding to rituximab have also been seen&#46; Patients with certain genotypes at the antibody binding site appear to respond better to treatment with rituximab and disease-free periods are longer&#46; This polymorphism in the expression of the CD20 antigen in malignant B cells may define a subgroup of patients with innate resistance to rituximab&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Recurrences after treatment with intravenous rituximab&#44; in both patients with FL and with MZL&#44; are frequent &#40;20&#37; and 50&#37;&#44; respectively&#41;&#46; However&#44; recurrences of CBCL are frequent with all treatment types except surgery and RT&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Thus&#44; authors such as Gellrich et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> propose more prolonged treatments of 8 cycles instead of 4&#44; as better response rates &#40;90&#37;&#41; and remission rates are obtained&#59; however&#44; the benefits of prolonging treatment are not clearly demonstrated due to the small number of patients studied&#46; In a subsequent study of 16 patients&#44; Valencak et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> reported complete response in 62&#37; of indolent CBCL treated with intravenous rituximab and proposed that 4 cycles would be sufficient&#46; The authors highlighted the lack of studies that support the need to extend treatment&#46; Likewise&#44; the published studies do not provide clear indications as to whether re-treatment with rituximab after recurrence might be beneficial&#44; as has been demonstrated in systemic FL&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;31</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Most studies define complete response as disappearance of all cutaneous lesions&#44; which are assessed clinically with regular follow-up of the patients&#46; Some studies have&#44; however&#44; also evaluated histologic response of the lesions<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;18&#44;25</span></a> by means of a skin biopsy after treatment&#46; These studies report the presence of an infiltrate of CD8-positive T cells&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> with decreased CD20 expression&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Gellrich et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> took biopsies from 8 of the treated patients with complete response and found that despite a complete clinical response&#44; only 6 had complete histologic response&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Intravenous treatment with rituximab is safe and generally well tolerated&#44; particularly in comparison with other traditional chemotherapeutic agents&#46; The adverse effects are summarized in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> The most frequently reported cutaneous effects are mild&#44; usually in the form of rash or urticaria&#44; which occur in approximately 15&#37; of patients&#46; Serious side effects such as paraneoplastic pemphigus or Steven-Johnson syndrome appear in fewer than 2&#37;&#46; Of interest is the occurrence of wheals around the skin lesions in FL treated with systemic rituximab&#59; this is thought to be due to the release of inflammatory cytokines&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;19</span></a> The risk of reactivation of hepatitis B virus is also of particular interest in patients with chronic infection as the event can potentially be fatal&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;33</span></a> The American Hepatology Guidelines recommend the use of lamivudine as prophylaxis for up to 6 months after finishing treatment with intravenous rituximab in carriers of HbsAg&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> Some authors suggest this prophylactic period should be extended to up to 2 years after finishing treatment&#44; given that late reactivation of hepatitis B has been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">In most studies&#44; intravenous rituximab is considered the treatment of choice for multifocal lesions and also for lesions on the face and scalp&#44; as RT may cause alopecia and irreversible cutaneous effects&#44; such as poichyloderma or atrophy&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;26</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In recent years&#44; the use of intralesional rituximab has become widespread for FL and MZL&#46; The aim is to make treatment more comfortable and accessible while minimizing side effects &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46; The published cases of treatment of FL and MZL with intralesional rituximab are summarized in <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;21&#44;35&#8211;40</span></a> The complete response rates with this treatment in indolent B-cell lymphomas are somewhat greater than those achieved with intravenous administration&#46; Response rates range from 83&#37; to 89&#37;&#44; but the recurrence rate after treatment remains high &#40;40&#37; to 62&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In most studies&#44; regimens of between 10 and 30<span class="elsevierStyleHsp" style=""></span>mg per lesion &#40;diluted to 10<span class="elsevierStyleHsp" style=""></span>mg&#47;mL&#41; are used&#44; up to 3 times a week and in cycles of up to 12 weeks&#44; according to response&#46; The most frequently reported side effect is injection-site pain&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;21&#44;35&#8211;39</span></a> Of particular note given the large number of patients included is a recent study published by the Spanish Cutaneous Lymphoma Group&#44; who retrospectively analyzed the outcomes of intralesional rituximab treatment of indolent cutaneous B-cell lymphoma in several hospitals&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> A total of 35 patients were included&#44; 17 with MZL and 18 with FL&#46; A mean of 2 lesions were treated per patient&#46; Most patients were treated with 3 injections per week for 1 week in every month&#46; A complete response rate of 74&#37; was found&#8212;slightly below that reported in previous studies&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Mean disease-free survival was 114 weeks&#46; Side effects were detected in 54&#37; of the patients&#44; with the most common being injection-site pain&#46; A small number of patients had fever presenting between 6 and 12 hours after the injection&#44; although the effect was transient and observed most often in the first injections&#46; Some of the most important findings in this study are that there were no apparent factors predictive of response or differences in responses according to underlying disease &#40;MZL or FL&#41;&#44; in contrast to the case when the drug is administered systemically&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The conclusion from these studies is that intralesional use of rituximab is becoming more widespread in selected patients with low-grade CBCL in view of the convenience&#44; lower dose&#44; and fewer side effects&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Cutaneous Diffuse Large B-cell Lymphoma&#44; Leg-Type</span><p id="par0075" class="elsevierStylePara elsevierViewall">CDLBCL-LT occurs less frequently than the other 2 types of CBCL discussed above&#46; This type accounts for approximately 1&#37; to 3&#37; of all primary cutaneous lymphomas and&#44; unlike FL and MZL&#44; follows a more aggressive course with frequent extracutaneous spread and recurrence after treatment&#46; Prognosis is intermediate with a 5-year survival rate of approximately 50&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Factors indicative of poor prognosis in cutaneous large B-cell lymphomas include onset at an early age&#44; ulceration&#44; and positive staining for multiple myeloma oncogene &#40;MUM&#41; 1 and bcl-2&#44; while expression of bcl-6 is associated with good prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> However&#44; these findings are open to debate because the series of cutaneous large B-cell lymphomas include some forms of FL&#44; which is typically bcl-6 positive and has a better prognosis&#46; In contrast&#44; CDLBCL-LT is typically MUM-1 positive and has a worse prognosis&#46; The expression of one of these proteins may not therefore be a prognostic factor in itself&#44; but rather related to diagnosis of 2 different lymphomas with different prognoses&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The guidelines for management of CBCL&#44; issued by the EORTC&#44; recommend treatment of CDLBCL-LT with polychemotherapy with or without rituximab &#40;cyclophosphamide&#44; hydroxydaunorubicin&#44; Oncovin&#44; prednisone &#91;CHOP&#93;-like or R-CHOP regimens&#41;&#46; In localized disease&#44; the recommended treatment is RT&#44; which shows good response rates&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> There are 25 cases in the literature of CDLBCL-LT treated with rituximab in monotherapy &#40;summarized in <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;16&#44;42&#8211;50</span></a> Regimens of 4 to 8 infusions were used with or without local RT in the tumors&#46; The complete response rate of the published cases is 48&#37;&#44; but this response is only maintained for more than 6 months in 4 of the patients&#44; that is&#44; 18&#37;&#44; and so recurrences after treatment are frequent &#40;82&#37;&#41;&#46; In all cases&#44; treatment was well tolerated&#44; without significant side effects&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The role of rituximab as monotherapy in CDLBCL-LT is not well defined&#59; the results reported in the literature suggest that there is a marked initial response but recurrences and disease progression are frequent&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The recommended treatment with CHOP or CHOP-like polychemotherapy in CDLBCL-LT obtains complete response rates of 81&#37;&#44; but once again recurrence rates are high at 54&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Some authors therefore recommend the use of intravenous rituximab as a less aggressive option that is better adapted to older patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;43&#44;45&#44;49</span></a> Despite the recommendations of the WHO-EORTC&#44; some authors have wondered whether intensified treatments with greater toxicity really improve prognosis in these patients&#46; Most suggest that the treatment of choice should be tailored and adapted to the age of the patient&#44; with rituximab considered as a palliative measure&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Other B-Cell Lymphoproliferative Processes</span><p id="par0095" class="elsevierStylePara elsevierViewall">There has been a report of a case of cutaneous intravascular large B-cell lymphoma treated with R-CHOP with complete clinical and histologic response maintained for 6 months&#46; These results appear promising&#44; as this is a very aggressive lymphoma&#46; However&#44; given the rarity of the condition&#44; it is difficult to establish treatment protocols&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">There is also a published case of pseudo-B-cell lymphoma refractory to conventional therapies that responded well to intralesional rituximab&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions</span><p id="par0105" class="elsevierStylePara elsevierViewall">Rituximab is an anti-CD20 antibody that is increasingly used in the treatment of CBCL&#46; Good response rates are obtained in indolent B-cell lymphomas&#44; FL&#44; and MZL&#44; for both the intravenous and intralesional route of administration&#44; although recurrence is frequent&#46; Rituximab is not the preferred treatment&#44; but it should be considered in patients with multiple and&#47;or recurrent lesions at visible sites where radiotherapy or surgery may leave sequelae or scars&#46; Intralesional use has become widespread in recent years with similar outcomes to intravenous use&#44; but with fewer side effects and a lower cost&#46; More studies are needed to establish the usefulness and the optimal protocol in other B-cell cutaneous lymphomas&#46; In the future&#44; molecular predictors of response&#44; new clinical trials&#44; and new combinations with existing treatments or other monoclonal antibodies may help define the role of rituximab in the treatment of CBCL&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Ethical Responsibilities</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">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 investigation&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Confidentiality of data</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors declare that they have followed their hospital&#39;s protocol on the publication of data concerning patients and that all patients included in the study have received sufficient information and have given their written informed consent to participate in the study&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Right to privacy and informed consent</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that patient data do not appear in this article&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of Interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Introduction"
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        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Rituximab"
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        6 => array:3 [
          "identificador" => "sec0015"
          "titulo" => "Rituximab in Primary Cutaneous Lymphomas"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Follicular Lymphoma and Marginal Zone Lymphoma"
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            1 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Cutaneous Diffuse Large B-cell Lymphoma&#44; Leg-Type"
            ]
            2 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Other B-Cell Lymphoproliferative Processes"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Conclusions"
        ]
        8 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Ethical Responsibilities"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Protection of human and animal subjects"
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            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Confidentiality of data"
            ]
            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Right to privacy and informed consent"
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          ]
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        9 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Conflicts of Interest"
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        10 => array:1 [
          "titulo" => "References"
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    "fechaRecibido" => "2012-05-27"
    "fechaAceptado" => "2012-10-25"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec324328"
          "palabras" => array:6 [
            0 => "Rituximab"
            1 => "Primary cutaneous B-cell lymphoma"
            2 => "Follicular lymphoma"
            3 => "Marginal zone lymphoma"
            4 => "Primary cutaneous diffuse large B-cell lymphoma leg type"
            5 => "Adverse effects"
          ]
        ]
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec324329"
          "palabras" => array:6 [
            0 => "Rituximab"
            1 => "Linfoma primario cut&#225;neo de c&#233;lulas B"
            2 => "Linfoma folicular"
            3 => "Linfoma de la zona marginal"
            4 => "Linfoma cut&#225;neo primario difuso de c&#233;lulas grandes tipo piernas"
            5 => "Efectos secundarios"
          ]
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        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen&#44; which is found in both normal and neoplastic B cells&#46; In recent years&#44; it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment &#40;radiotherapy and surgery&#41; of 2 types of indolent lymphoma&#44; namely&#44; primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma&#46; Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma&#44; leg type&#46; Its use as an alternative drug led to it being administered intralesionally&#44; with beneficial effects&#46; In the present article&#44; we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Rituximab es un anticuerpo quim&#233;rico murino-humano dirigido contra el ant&#237;geno CD20 presente en los linfocitos B normales y neopl&#225;sicos&#46; Su uso en los linfomas cut&#225;neos de c&#233;lulas B ha ido en creciente desarrollo en los &#250;ltimos a&#241;os&#46; As&#237; se plantea como una alternativa a los tratamientos cl&#225;sicos de radioterapia y cirug&#237;a en los linfomas de curso indolente&#44; el linfoma folicular y el linfoma de la zona marginal&#46; Tambi&#233;n se utiliza en el tratamiento del linfoma cut&#225;neo primario de c&#233;lulas grandes tipo piernas como alternativa a la poliquimioterapia&#46; Su desarrollo como alternativa terap&#233;utica ha llevado a su uso intralesional tambi&#233;n con buenos resultados&#46; En este art&#237;culo se revisa la literatura publicada del uso de rituximab en los linfomas cut&#225;neos primarios de c&#233;lulas B&#46;</p>"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Fern&#225;ndez-Guarino M&#44; Ortiz-Romero PL&#44; Fern&#225;ndez-Misa R&#44; Montalb&#225;n C&#46; Rituximab en el tratamiento de los linfomas cut&#225;neos B primarios&#58; revisi&#243;n&#46; Actas Dermosifiliogr&#46; 2014&#59;105&#58;438&#8211;445&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Image of a patient with marginal zone lymphoma in the leg&#46;</p>"
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      ]
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        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 590
            "Ancho" => 801
            "Tamanyo" => 80534
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Resolution after 3 injections&#44; each a week apart&#44; of intralesional rituximab &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;mL&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Willemze et al&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and Cerroni et al&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; CT&#44; chemotherapy&#59; FL&#44; follicular lymphoma&#59; IFN-&#945;&#44; interferon alfa&#59; IgH&#44; immunoglobulin H&#59; IHC&#44; immunohistochemistry&#59; CDLBCL-LT&#44; cutaneous diffuse large B-cell lymphoma leg-type&#59; MZL&#44; marginal zone lymphoma&#59; RT&#44; radiotherapy&#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"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">MFZ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">FL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">CDLBCL-LT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical Characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Young adults or adultsSingle or multiple plaques or tumors on the legsFrequent cutaneous recurrencesSometimes associated with <span class="elsevierStyleItalic">Borrelia burgdorferi</span> infectionExtracutaneous involvement uncommon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AdultsSolitary tumors or clusters of tumors on the head and trunkCutaneous recurrence in 20&#37;Extracutaneous spread in 5&#37; to 10&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Single or multiple tumors on the legs&#59; rarely present at other sitesFrequent cutaneous recurrencesFrequent extracutaneous spread&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Histopathology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diffuse or patchy infiltrate of small B cellsIncludes cells in marginal zone &#40;centrocyte-like&#41;&#44; lymphoplasmacytoid and plasma cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Follicular or diffuse infiltrate or bothCentrocytes and centroblasts&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infiltrated monomorphous with predominance of centroblasts and immunoblasts&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IHC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CD79a&#43;&#44; Bcl-2&#43;&#44; Bcl-6-&#44; CD10-&#44; cyclin D1-&#44; CD5-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CD20&#43;&#44; CD79a&#43;&#44; Bcl2-&#44; Bcl- 6&#43;&#44; MUM1-&#44; CD10<span class="elsevierStyleSup">&#177;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CD20&#43;&#44; CD79a&#43;&#44; Bcl-6<span class="elsevierStyleSup">&#177;</span>&#44; CD10-&#44; Bcl-2&#43;&#44; MUM-1&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clonal rearrangement of IgH 50&#37; to 60&#37;t&#40;14-18&#41; in a small percentage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IgH clonal rearrangementt&#40;14&#59;18&#41; absent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clonal rearrangement of IgH in most casest&#40;9&#58;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RT&#44; surgery&#44; IFN-&#945;&#44; rituximabSystemic CT reserved for generalized lesions or extracutaneous involvement &#40;CHOP&#44; R-CHOP&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RT&#44; surgery&#44; IFN-&#945;&#44; rituximabSystemic CT reserved for generalized lesions or extracutaneous involvement&#40;CHOP&#44; R-CHOP&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RT for solitary lesionsPolychemotherapy&#58; CHOP&#44; R-CHOPRituximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5-year survival&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab508518.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the Most Common Primary Cutaneous B-Cell Lymphomas&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Heinzerling et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and Brunet-Posenti et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; CR&#44; complete response&#59; NS&#44; not specified&#59; PR&#44; partial response&#59; RT&#44; radiotherapy&#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"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Author&#47;Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Number of Patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Number of Infusions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Duration of Response&#44; mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Remarks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Heinzerling 2000<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44; 2&#44; 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 PR&#47;1 CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44; 12&#44; 10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Urticarial reaction in the tumorsDisappearance of B cells from peripheral blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gellrich 2001<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4-8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kennedy 2004<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PR&#44; CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44; 7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lacouture 2005<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment of recurrence after RT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fink-Puches 2005<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44; 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&#44; CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#44; 14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">One patient had cutaneous recurrence at a different site&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gellrich 2005<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8-10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 CR&#44; 2 PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7-30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shows histological cure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Errante 2006<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Urticarial reaction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gitelson 2006<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17-39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">One of these&#44; maintenance therapy every 2 months for 8 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kerl 2006<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No recurrence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Morales 2008<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 CR&#44; 2 PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6-31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maintenance&#44; variable for each patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Valencak 2009<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6-57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment of multifocal lesions&#44; not candidates for RT or surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brunet-Posenti 2011<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Edematous infusion reaction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1-10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 CR&#47;10 PR77&#37; CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6-57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab508521.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Published Cases of Follicular Lymphoma Treated with Intravenous Rituximab&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Gellrich et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#59; Gellrich et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#59; Kerl et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#59; Morales et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#59; Valencak et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#59; Soda et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#59; and Seker et al&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; CR&#44; complete response&#59; IR&#44; incomplete response&#59; PR&#44; partial response&#59; SD&#44; stable disease&#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"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Author&#47;Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Number of Patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Number of Infusions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Duration of Response&#44; mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Remarks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soda 2001<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple lesions&#44; rituximab used first-line&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gellrich 2001<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4-8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maintenance treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gellrich 2005<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recurrence after 23 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kerl 2006<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No recurrence&#44; no maintenance therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Morales 2008<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4-6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 CR&#44; 2 PR&#44; 1 SD&#44; 1 IR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6-23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maintenance treatment in 3 of the patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Valencak 2009<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4-6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 CR&#44; 1 PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17-75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Additional treatment in 2 of the patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Seker 2010<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All multinodular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab508519.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Published Cases of Marginal Zone Lymphoma Treated with Intravenous Rituximab&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Fink-Puches et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#59; Kerl et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#59; Heinzerling et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#59; Paul et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&#59; Roguedas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&#59; Kyrtsonis et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#59; Park et al&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>&#59; and Pe&#241;ate et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; CR&#44; complete response&#59; FL&#44; follicular lymphoma&#59; MZL&#44; marginal zone lymphoma&#59; PR&#44; partial response&#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"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Number of Lesions&#47;Type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Prior Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Duration of Response&#44; mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Recurrence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Heinzerling 2000<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 FL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0-12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paul 2001<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 FL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fink-Puches 2005<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 FL&#47;4 MZL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#47;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 CR&#47;1 PR &#40;MZL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12-27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;3 MZL&#44; 1 FL&#41;&#47;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Roguedas 2005<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 FL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kerl 2005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 FL&#47;3 MZL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3-14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;1 FL&#44; 1 MZL&#41;&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kyrtsonis 2006<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 MZL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36-44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Park 2010<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 MZL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pe&#241;ate 2012<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 FL&#47;17 MZL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#47;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#47;18 CR in FL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3-48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#47;14 CR in FL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#47;17 CR in MZL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#47;11 CR in MZL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab508516.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Pediatric case&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Published Cases of Follicular Lymphoma Treated with Intralesional Rituximab&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Scheinfield<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cutaneous Effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RashPruritusUrticariaBacterial infectionsLichenoid reactionsParaneoplastic pemphigusSteven-Johnson syndrome&#47;toxic epidermal necrosisVesicular&#47;blistering dermatitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systemic Effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fatal infusion reaction &#40;first 24<span class="elsevierStyleHsp" style=""></span>h&#41;Tumor lysis syndromeHepatitis B reactivation &#40;can be fulminant&#41;Severe cardiac arrhythmiasRenal failure &#40;can be fatal&#41;Hypersensitivity reactionsOthers&#58; sick serum disease&#44; rheumatoid-like inflammatory arthritis syndrome&#44; vasculitis&#44; mucositis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab508520.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Adverse Effects of Systemic Rituximab&#46;</p>"
        ]
      ]
      7 => array:7 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Lacouture et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#59; Gellrich et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#59; Heinzerling et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#59; Sabroe et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&#59; Aboulafia<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a>&#59; Garbea et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a>&#59; Bonnekoh et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a>&#59; Viguier et al&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a>&#59; Zinzani et al&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a>&#59; Brogan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a>&#59; Pedraz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a>&#59; and Fenot et al&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a></p><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; CR&#44; complete response&#59; CT&#44; chemotherapy&#59; NS&#44; not specified&#59; PD&#44; progressive disease&#59; PR&#44; partial response&#59; RT&#44; radiotherapy&#59; SD&#44; stable disease</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"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Author&#47;Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Number of Patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Number of Infusions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Duration of Response&#44; mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Remarks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Heinzerling 2000<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 CR&#47;2 PR&#47;2 PD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6-13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No side effects of note&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sabroe 2000<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cycle repeated&#44; but recurrence after 3 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aboulafia 2001<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No side effects of note &#40;RT and polyCT avoided&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Garbea 2002<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adverse effects&#58; fever&#44; herpes zoster&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bonnekoh 2002<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No side effects of note &#40;RT and polyCT avoided&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Viguier 2002<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recurrence&#44; treated with R-CHOP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zinzani 2003<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No side effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brogan 2003<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 CR&#47;2 PD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Combined with RT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gellrich 2005<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lacouture 2005<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recurrence after RT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pedraz 2005<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not specified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fenot 2010<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 CR&#47;3 PR&#47;3 PD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26-28 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 patients retreated with R-CHOP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab508517.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Cutaneous Diffuse Large B-Cell Lymphoma Leg-Type&#44; Treated With Rituximab Monotherapy&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:52 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "WHO-EORTC classification for cutaneous lymphomas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Willemze"
                            1 => "E&#46;S&#46; Jaffe"
                            2 => "G&#46; Burg"
                            3 => "L&#46; Cerroni"
                            4 => "E&#46; Berti"
                            5 => "S&#46;H&#46; Swendlow"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2004-09-3502"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2005"
                        "volumen" => "105"
                        "paginaInicial" => "3768"
                        "paginaFinal" => "3785"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15692063"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Primary cutaneous B-cell lymphoma&#58; classification and treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46; Willemze"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Curr Opin Oncol"
                        "fecha" => "2006"
                        "volumen" => "16"
                        "paginaInicial" => "425"
                        "paginaFinal" => "431"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "European Organization for Research and Treatment of Cancer and International Society of Cutaneous Lymphoma consensus recommendations for the manegement of cutaneous B-cell lymphomas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Senff"
                            1 => "E&#46; Noordijk"
                            2 => "Y&#46; Kim"
                            3 => "M&#46; Bagot"
                            4 => "E&#46; Berti"
                            5 => "L&#46; Cerroni"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2008-04-152850"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2008"
                        "volumen" => "112"
                        "paginaInicial" => "1600"
                        "paginaFinal" => "1609"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18567836"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The illustrated guide of skin lymphoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46; Cerroni"
                            1 => "K&#46; Gatter"
                            2 => "H&#46; Kerl"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "edicion" => "3rd ed&#46;"
                        "fecha" => "2011"
                        "editorial" => "Willey-Blackwell"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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Información de la revista
Vol. 105. Núm. 5.
Páginas 438-445 (junio 2014)
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8436
Vol. 105. Núm. 5.
Páginas 438-445 (junio 2014)
Review
Acceso a texto completo
Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review
Rituximab en el tratamiento de los linfomas cutáneos B primarios: revisión
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8436
M. Fernández-Guarinoa,
Autor para correspondencia
montsefdez@msn.com

Corresponding author.
, P.L. Ortiz-Romerob, R. Fernández-Misac, C. Montalbánd
a Servicio de Dermatología, Hospital Central de la Cruz Roja, Universidad Alfonso X El Sabio, Madrid, Spain
b Facultad de Medicina, Universidad Complutense, Instituto i+12, Hospital Universitario 12 de Octubre, Madrid, Spain
c Servicio de Dermatología, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
d Servicio de Medicina Interna, Hospital Universitario Ramón y Cajal, Madrid, Spain
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Tablas (6)
Table 1. Characteristics of the Most Common Primary Cutaneous B-Cell Lymphomas.
Table 2. Published Cases of Follicular Lymphoma Treated with Intravenous Rituximab.
Table 3. Published Cases of Marginal Zone Lymphoma Treated with Intravenous Rituximab.
Table 4. Published Cases of Follicular Lymphoma Treated with Intralesional Rituximab.
Table 5. Adverse Effects of Systemic Rituximab.
Table 6. Cutaneous Diffuse Large B-Cell Lymphoma Leg-Type, Treated With Rituximab Monotherapy.
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Abstract

Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma.

Keywords:
Rituximab
Primary cutaneous B-cell lymphoma
Follicular lymphoma
Marginal zone lymphoma
Primary cutaneous diffuse large B-cell lymphoma leg type
Adverse effects
Resumen

Rituximab es un anticuerpo quimérico murino-humano dirigido contra el antígeno CD20 presente en los linfocitos B normales y neoplásicos. Su uso en los linfomas cutáneos de células B ha ido en creciente desarrollo en los últimos años. Así se plantea como una alternativa a los tratamientos clásicos de radioterapia y cirugía en los linfomas de curso indolente, el linfoma folicular y el linfoma de la zona marginal. También se utiliza en el tratamiento del linfoma cutáneo primario de células grandes tipo piernas como alternativa a la poliquimioterapia. Su desarrollo como alternativa terapéutica ha llevado a su uso intralesional también con buenos resultados. En este artículo se revisa la literatura publicada del uso de rituximab en los linfomas cutáneos primarios de células B.

Palabras clave:
Rituximab
Linfoma primario cutáneo de células B
Linfoma folicular
Linfoma de la zona marginal
Linfoma cutáneo primario difuso de células grandes tipo piernas
Efectos secundarios
Texto completo
Introduction

Primary cutaneous B-cell lymphomas (CBCLs) are a group of B-cell lymphomas localized in the skin at the time of diagnosis. According to the recent World Health Organization (WHO)-European Organization for Research and Treatment of Cancer (EORTC) classification, there are 3 main subgroups: follicular lymphoma (FL), marginal zone lymphoma (MZL), and cutaneous diffuse large B-cell lymphoma leg-type (CDLBCL-LT).1 These account for approximately 20% to 25% of all primary cutaneous lymphomas. Most CBLCs (more than 80%) correspond to the 2 variants with an indolent course, FL and MZL.2 The main characteristics of these 3 subgroups are summarized in Table 1.3 Neither FL nor MZL follows a very aggressive course, and 5-year survival is greater than 95%.1 Although prognosis is excellent, recurrence rates after treatment are high, ranging from 14% to 62%.3 FL and MZL most frequently present as plaque or nodular lesions, occasionally with an anatomic distribution, with the trunk being the most frequent site (48.9%), followed by the face (26.4%).4,5 Given the benign course of these cutaneous B-cell lymphomas and their frequent multifocal distribution, a conservative approach to treatment should be followed. The most widely used types of treatment are radiotherapy (RT) and surgery,4,5 though these carry with them a risk of sequelae and are not ideal in the case of multifocal and/or recurrent lesions. Other therapeutic options therefore need to be explored. In absence of controlled clinical trials, there is no clear consensus on the best treatment for indolent CBCL.3 CDLBCL-LT in contrast follows a rapidly progressing course with a high rate of recurrence and a tendency for extracutaneous dissemination; 5-year survival is 50%.3 The lesions are located on the legs in more than 70% of patients, with presentation in the form of nodules or ulcerated tumors. Differential diagnosis should include systemic diffuse large cell non-Hodgkin lymphoma (NHL) with cutaneous involvement.6 In recent years, systemic rituximab alone or in combination with chemotherapeutic agents has been introduced for the treatment of CDLBCL-LT.

Table 1.

Characteristics of the Most Common Primary Cutaneous B-Cell Lymphomas.

  MFZ  FL  CDLBCL-LT 
Clinical Characteristics  Young adults or adultsSingle or multiple plaques or tumors on the legsFrequent cutaneous recurrencesSometimes associated with Borrelia burgdorferi infectionExtracutaneous involvement uncommon  AdultsSolitary tumors or clusters of tumors on the head and trunkCutaneous recurrence in 20%Extracutaneous spread in 5% to 10%  Single or multiple tumors on the legs; rarely present at other sitesFrequent cutaneous recurrencesFrequent extracutaneous spread 
Histopathology  Diffuse or patchy infiltrate of small B cellsIncludes cells in marginal zone (centrocyte-like), lymphoplasmacytoid and plasma cells  Follicular or diffuse infiltrate or bothCentrocytes and centroblasts  Infiltrated monomorphous with predominance of centroblasts and immunoblasts 
IHC  CD79a+, Bcl-2+, Bcl-6-, CD10-, cyclin D1-, CD5-  CD20+, CD79a+, Bcl2-, Bcl- 6+, MUM1-, CD10±  CD20+, CD79a+, Bcl-6±, CD10-, Bcl-2+, MUM-1+ 
Genetics  Clonal rearrangement of IgH 50% to 60%t(14-18) in a small percentage  IgH clonal rearrangementt(14;18) absent  Clonal rearrangement of IgH in most casest(9:21) 
Treatment  RT, surgery, IFN-α, rituximabSystemic CT reserved for generalized lesions or extracutaneous involvement (CHOP, R-CHOP)  RT, surgery, IFN-α, rituximabSystemic CT reserved for generalized lesions or extracutaneous involvement(CHOP, R-CHOP)  RT for solitary lesionsPolychemotherapy: CHOP, R-CHOPRituximab 
5-year survival  >95%  95%  50% 

Source: Willemze et al.1 and Cerroni et al.4

Abbreviations: CT, chemotherapy; FL, follicular lymphoma; IFN-α, interferon alfa; IgH, immunoglobulin H; IHC, immunohistochemistry; CDLBCL-LT, cutaneous diffuse large B-cell lymphoma leg-type; MZL, marginal zone lymphoma; RT, radiotherapy.

Rituximab

Rituximab is a murine-human chimeric monoclonal immunoglobulin G antibody against the CD20 antigen present on almost all neoplastic and normal B-cells. It has been used successfully in the treatment of systemic B-cell NHL either as monotherapy or more commonly in combination with other chemotherapeutic agents.7 In recent years, rituximab has been used by dermatologists with good outcomes in a range of skin diseases8 and CBCLs.

In vitro studies of rituximab have shown this agent induces lysis of lymphoma B-cells by antibody-dependent cell mediated cytotoxicity, complement activation, and direct induction of apoptosis. This mechanism does not depend on the immune system and occurs because the variable region of murine origin binds with high affinity to the CD20 antigen expressed on malignant B lymphocytes, halting their proliferation and inducing apoptosis probably through transmembrane calcium channels.6 Rituximab has also been shown to induce an antigen-specific response in T cells by an immunization mechanism.9 Additionally the drug is able to sensitize cells to the cytotoxic effects of other chemotherapeutic agents.10

Rituximab is also known to act via the bcl-2 protein. This marker is overexpressed in 85% of CDLBCL-LT and is considered one of the factors associated with worse prognosis.11 In the case of systemic diffuse large cell lymphomas, the addition of rituximab to combinations based on anthracyclines is particularly beneficial for bcl-2 positive lymphomas, which had a worse prognosis before rituximab was available.12

Rituximab in Primary Cutaneous LymphomasFollicular Lymphoma and Marginal Zone Lymphoma

Primary cutaneous FL and MZL are cutaneous lymphomas with an indolent course despite the high rates of recurrence. It is therefore important to highlight that treatment should not be aggressive in most cases. The recommendations for management of LF and MZL include withholding treatment (watchful waiting), RT, surgery, or intralesional interferon alfa.3 Sometimes, however, large, painful, disfiguring, or itchy multiple lesions may be present; watchful waiting is not an option and treatment should be administered. Moreover, in these situations, local skin interventions, such as surgery or RT, are not appropriate, particularly in the case of multiple lesions or lesions on sites such as the face or neck where the interventions might leave substantial esthetic sequelae. In these circumstances, other treatment alternatives, among them systemic or intralesional rituximab, have been used.

Tables 2 and 3 summarize the published cases of FL and MZL, respectively, treated with systemic rituximab. Table 4 summarizes the cases of FL and MZL treated with intralesional administration of rituximab.

Table 2.

Published Cases of Follicular Lymphoma Treated with Intravenous Rituximab.

Author/Year  Number of Patients  Number of Infusions  Response  Duration of Response, mo  Remarks 
Heinzerling 200013  1, 2, 4  2 PR/1 CR  5, 12, 10  Urticarial reaction in the tumorsDisappearance of B cells from peripheral blood 
Gellrich 200114  4-8  PR   
Kennedy 200415  PR, CR  6, 7   
Lacouture 200516  CR  24  Treatment of recurrence after RT 
Fink-Puches 200517  3, 4  CR, CR  24, 14  One patient had cutaneous recurrence at a different site 
Gellrich 200518  8-10  6 CR, 2 PR  7-30  Shows histological cure 
Errante 200619  CR  NS  Urticarial reaction 
Gitelson 200620  CR  17-39  One of these, maintenance therapy every 2 months for 8 months 
Kerl 200621  CR  18  No recurrence 
Morales 200822  10  8 CR, 2 PR  6-31  Maintenance, variable for each patient 
Valencak 200923  11  CR  6-57  Treatment of multifocal lesions, not candidates for RT or surgery 
Brunet-Posenti 201124  CR  NS  Edematous infusion reaction 
Total  44  1-10  34 CR/10 PR77% CR  6-57   

Source: Heinzerling et al.13 and Brunet-Posenti et al.24

Abbreviations: CR, complete response; NS, not specified; PR, partial response; RT, radiotherapy.

Table 3.

Published Cases of Marginal Zone Lymphoma Treated with Intravenous Rituximab.

Author/Year  Number of Patients  Number of Infusions  Response  Duration of Response, mo  Remarks 
Soda 200125  PR  Multiple lesions, rituximab used first-line 
Gellrich 200114  4-8  PR  Maintenance treatment 
Gellrich 200518  PR  23  Recurrence after 23 months 
Kerl 200621  CR  24  No recurrence, no maintenance therapy 
Morales 200822  4-6  1 CR, 2 PR, 1 SD, 1 IR  6-23  Maintenance treatment in 3 of the patients 
Valencak 200923  4-6  4 CR, 1 PR  17-75  Additional treatment in 2 of the patients 
Seker 201026  CR  13  All multinodular 

Source: Gellrich et al.14; Gellrich et al.18; Kerl et al.21; Morales et al.22; Valencak et al.23; Soda et al.25; and Seker et al.26

Abbreviations: CR, complete response; IR, incomplete response; PR, partial response; SD, stable disease.

Table 4.

Published Cases of Follicular Lymphoma Treated with Intralesional Rituximab.

Author  Number of Lesions/Type  Prior Treatment  Response  Duration of Response, mo  Recurrence 
Heinzerling 200013  2 FL  2/2  2 PR  0-12  2/2 
Paul 200136  2 FL  1/2  2 CR  12  0/2 
Fink-Puches 200517  3 FL/4 MZL  1/7  6 CR/1 PR (MZL)  12-27  4 (3 MZL, 1 FL)/7 
Roguedas 200537  1 FL  1/1  CR  12  1/1 
Kerl 2005  3 FL/3 MZL  4/6  6 CR  3-14  2 (1 FL, 1 MZL)/6 
Kyrtsonis 200638  2 MZL  0/2  2 CR  36-44  2/2 
Park 201039,a  1 MZL  0/1  CR  26  0/1 
Peñate 201240  18 FL/17 MZL  25/35  14/18 CR in FL  3-48  6/14 CR in FL 
      11/17 CR in MZL    4/11 CR in MZL 

Source: Fink-Puches et al.17; Kerl et al.21; Heinzerling et al.35; Paul et al.36; Roguedas et al.37; Kyrtsonis et al.38; Park et al.39; and Peñate et al.40

Abbreviations: CR, complete response; FL, follicular lymphoma; MZL, marginal zone lymphoma; PR, partial response.

a

Pediatric case.

In total, 44 cases have been published of cutaneous FL treated with intravenous rituximab (Table 2).13–24 Regimens have ranged from the usual 4 infusions, once a week, with standard doses of 375mg/m2 to courses of up to 10 infusions. The complete response rate for all the published cases is approximately 77%, with a response duration ranging from 6 to 57 months. For MZL, 16 cases of systemic rituximab treatment have been published (Table 3),14,18,21,25,26 with an overall complete response rate of 43% and a duration of response of between 6 and 75 months.

This apparently worse response to rituximab in patients with MZL is pending confirmation in the future in large prospective studies; if real, the difference could be due to several mechanisms that confer resistance to rituximab. A study has been published describing the lack of efficacy of rituximab in patients with noncutaneous MZL who also received chemoimmunotherapy.27 One of the hypotheses is that malignant B cells acquire new mutations that confer resistance to rituximab-induced apoptosis. Thus, in a study of 4 patients with recurrent disease, an increase in bcl-2 activity was observed after rituximab treatment.28 Variations in the site of B-cell binding to rituximab have also been seen. Patients with certain genotypes at the antibody binding site appear to respond better to treatment with rituximab and disease-free periods are longer. This polymorphism in the expression of the CD20 antigen in malignant B cells may define a subgroup of patients with innate resistance to rituximab.29

Recurrences after treatment with intravenous rituximab, in both patients with FL and with MZL, are frequent (20% and 50%, respectively). However, recurrences of CBCL are frequent with all treatment types except surgery and RT.3 Thus, authors such as Gellrich et al.18 propose more prolonged treatments of 8 cycles instead of 4, as better response rates (90%) and remission rates are obtained; however, the benefits of prolonging treatment are not clearly demonstrated due to the small number of patients studied. In a subsequent study of 16 patients, Valencak et al.23 reported complete response in 62% of indolent CBCL treated with intravenous rituximab and proposed that 4 cycles would be sufficient. The authors highlighted the lack of studies that support the need to extend treatment. Likewise, the published studies do not provide clear indications as to whether re-treatment with rituximab after recurrence might be beneficial, as has been demonstrated in systemic FL.30,31

Most studies define complete response as disappearance of all cutaneous lesions, which are assessed clinically with regular follow-up of the patients. Some studies have, however, also evaluated histologic response of the lesions14,18,25 by means of a skin biopsy after treatment. These studies report the presence of an infiltrate of CD8-positive T cells,14 with decreased CD20 expression.25 Gellrich et al.18 took biopsies from 8 of the treated patients with complete response and found that despite a complete clinical response, only 6 had complete histologic response.

Intravenous treatment with rituximab is safe and generally well tolerated, particularly in comparison with other traditional chemotherapeutic agents. The adverse effects are summarized in Table 5.32 The most frequently reported cutaneous effects are mild, usually in the form of rash or urticaria, which occur in approximately 15% of patients. Serious side effects such as paraneoplastic pemphigus or Steven-Johnson syndrome appear in fewer than 2%. Of interest is the occurrence of wheals around the skin lesions in FL treated with systemic rituximab; this is thought to be due to the release of inflammatory cytokines.13,19 The risk of reactivation of hepatitis B virus is also of particular interest in patients with chronic infection as the event can potentially be fatal.26,33 The American Hepatology Guidelines recommend the use of lamivudine as prophylaxis for up to 6 months after finishing treatment with intravenous rituximab in carriers of HbsAg.34 Some authors suggest this prophylactic period should be extended to up to 2 years after finishing treatment, given that late reactivation of hepatitis B has been reported.26

Table 5.

Adverse Effects of Systemic Rituximab.

Cutaneous Effects  RashPruritusUrticariaBacterial infectionsLichenoid reactionsParaneoplastic pemphigusSteven-Johnson syndrome/toxic epidermal necrosisVesicular/blistering dermatitis 
Systemic Effects  Fatal infusion reaction (first 24h)Tumor lysis syndromeHepatitis B reactivation (can be fulminant)Severe cardiac arrhythmiasRenal failure (can be fatal)Hypersensitivity reactionsOthers: sick serum disease, rheumatoid-like inflammatory arthritis syndrome, vasculitis, mucositis 

Source: Scheinfield32

In most studies, intravenous rituximab is considered the treatment of choice for multifocal lesions and also for lesions on the face and scalp, as RT may cause alopecia and irreversible cutaneous effects, such as poichyloderma or atrophy.19,26

In recent years, the use of intralesional rituximab has become widespread for FL and MZL. The aim is to make treatment more comfortable and accessible while minimizing side effects (Figs. 1 and 2). The published cases of treatment of FL and MZL with intralesional rituximab are summarized in Table 6.17,21,35–40 The complete response rates with this treatment in indolent B-cell lymphomas are somewhat greater than those achieved with intravenous administration. Response rates range from 83% to 89%, but the recurrence rate after treatment remains high (40% to 62%).3 In most studies, regimens of between 10 and 30mg per lesion (diluted to 10mg/mL) are used, up to 3 times a week and in cycles of up to 12 weeks, according to response. The most frequently reported side effect is injection-site pain.17,21,35–39 Of particular note given the large number of patients included is a recent study published by the Spanish Cutaneous Lymphoma Group, who retrospectively analyzed the outcomes of intralesional rituximab treatment of indolent cutaneous B-cell lymphoma in several hospitals.40 A total of 35 patients were included, 17 with MZL and 18 with FL. A mean of 2 lesions were treated per patient. Most patients were treated with 3 injections per week for 1 week in every month. A complete response rate of 74% was found—slightly below that reported in previous studies.3 Mean disease-free survival was 114 weeks. Side effects were detected in 54% of the patients, with the most common being injection-site pain. A small number of patients had fever presenting between 6 and 12 hours after the injection, although the effect was transient and observed most often in the first injections. Some of the most important findings in this study are that there were no apparent factors predictive of response or differences in responses according to underlying disease (MZL or FL), in contrast to the case when the drug is administered systemically.

Figure 1.

Image of a patient with marginal zone lymphoma in the leg.

(0.1MB).
Figure 2.

Resolution after 3 injections, each a week apart, of intralesional rituximab (10mg/mL).

(0.08MB).
Table 6.

Cutaneous Diffuse Large B-Cell Lymphoma Leg-Type, Treated With Rituximab Monotherapy.

Author/Year  Number of Patients  Number of Infusions  Response  Duration of Response, mo  Remarks 
Heinzerling 200013  1 CR/2 PR/2 PD  6-13  No side effects of note 
Sabroe 200042  PR  3 months  Cycle repeated, but recurrence after 3 weeks 
Aboulafia 200143  CR  NS  No side effects of note (RT and polyCT avoided) 
Garbea 200244  PD  0 months  Adverse effects: fever, herpes zoster 
Bonnekoh 200245  CR  8 months  No side effects of note (RT and polyCT avoided) 
Viguier 200246  CR  15 months  Recurrence, treated with R-CHOP 
Zinzani 200347  CR  8 months  No side effects 
Brogan 200348  1 CR/2 PD  6 months  Combined with RT 
Gellrich 200518  PD  0 months   
Lacouture 200516  CR  17 months  Recurrence after RT 
Pedraz 200549  CR  Not specified   
Fenot 201050  3 CR/3 PR/3 PD  26-28 months  5 patients retreated with R-CHOP 

Source: Lacouture et al.16; Gellrich et al.18; Heinzerling et al.35; Sabroe et al.42; Aboulafia43; Garbea et al.44; Bonnekoh et al.45; Viguier et al.46; Zinzani et al.47; Brogan et al.48; Pedraz et al.49; and Fenot et al.50

Abbreviations: CR, complete response; CT, chemotherapy; NS, not specified; PD, progressive disease; PR, partial response; RT, radiotherapy; SD, stable disease

The conclusion from these studies is that intralesional use of rituximab is becoming more widespread in selected patients with low-grade CBCL in view of the convenience, lower dose, and fewer side effects.

Cutaneous Diffuse Large B-cell Lymphoma, Leg-Type

CDLBCL-LT occurs less frequently than the other 2 types of CBCL discussed above. This type accounts for approximately 1% to 3% of all primary cutaneous lymphomas and, unlike FL and MZL, follows a more aggressive course with frequent extracutaneous spread and recurrence after treatment. Prognosis is intermediate with a 5-year survival rate of approximately 50%.3 Factors indicative of poor prognosis in cutaneous large B-cell lymphomas include onset at an early age, ulceration, and positive staining for multiple myeloma oncogene (MUM) 1 and bcl-2, while expression of bcl-6 is associated with good prognosis.41 However, these findings are open to debate because the series of cutaneous large B-cell lymphomas include some forms of FL, which is typically bcl-6 positive and has a better prognosis. In contrast, CDLBCL-LT is typically MUM-1 positive and has a worse prognosis. The expression of one of these proteins may not therefore be a prognostic factor in itself, but rather related to diagnosis of 2 different lymphomas with different prognoses.

The guidelines for management of CBCL, issued by the EORTC, recommend treatment of CDLBCL-LT with polychemotherapy with or without rituximab (cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone [CHOP]-like or R-CHOP regimens). In localized disease, the recommended treatment is RT, which shows good response rates.3 There are 25 cases in the literature of CDLBCL-LT treated with rituximab in monotherapy (summarized in Table 6).13,16,42–50 Regimens of 4 to 8 infusions were used with or without local RT in the tumors. The complete response rate of the published cases is 48%, but this response is only maintained for more than 6 months in 4 of the patients, that is, 18%, and so recurrences after treatment are frequent (82%). In all cases, treatment was well tolerated, without significant side effects.

The role of rituximab as monotherapy in CDLBCL-LT is not well defined; the results reported in the literature suggest that there is a marked initial response but recurrences and disease progression are frequent.

The recommended treatment with CHOP or CHOP-like polychemotherapy in CDLBCL-LT obtains complete response rates of 81%, but once again recurrence rates are high at 54%.3 Some authors therefore recommend the use of intravenous rituximab as a less aggressive option that is better adapted to older patients.16,43,45,49 Despite the recommendations of the WHO-EORTC, some authors have wondered whether intensified treatments with greater toxicity really improve prognosis in these patients. Most suggest that the treatment of choice should be tailored and adapted to the age of the patient, with rituximab considered as a palliative measure.

Other B-Cell Lymphoproliferative Processes

There has been a report of a case of cutaneous intravascular large B-cell lymphoma treated with R-CHOP with complete clinical and histologic response maintained for 6 months. These results appear promising, as this is a very aggressive lymphoma. However, given the rarity of the condition, it is difficult to establish treatment protocols.51

There is also a published case of pseudo-B-cell lymphoma refractory to conventional therapies that responded well to intralesional rituximab.52

Conclusions

Rituximab is an anti-CD20 antibody that is increasingly used in the treatment of CBCL. Good response rates are obtained in indolent B-cell lymphomas, FL, and MZL, for both the intravenous and intralesional route of administration, although recurrence is frequent. Rituximab is not the preferred treatment, but it should be considered in patients with multiple and/or recurrent lesions at visible sites where radiotherapy or surgery may leave sequelae or scars. Intralesional use has become widespread in recent years with similar outcomes to intravenous use, but with fewer side effects and a lower cost. More studies are needed to establish the usefulness and the optimal protocol in other B-cell cutaneous lymphomas. In the future, molecular predictors of response, new clinical trials, and new combinations with existing treatments or other monoclonal antibodies may help define the role of rituximab in the treatment of CBCL.

Ethical ResponsibilitiesProtection of human and animal subjects

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

Confidentiality of data

The authors declare that they have followed their hospital's protocol on the publication of data concerning patients and that all patients included in the study have received sufficient information and have given their written informed consent to participate in the study.

Right to privacy and informed consent

The authors declare that patient data do not appear in this article.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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Please cite this article as: Fernández-Guarino M, Ortiz-Romero PL, Fernández-Misa R, Montalbán C. Rituximab en el tratamiento de los linfomas cutáneos B primarios: revisión. Actas Dermosifiliogr. 2014;105:438–445.

Copyright © 2012. Elsevier España, S.L. and AEDV
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