Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100mg/m2 seems sufficient

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"aff0015" ] 3 => array:3 [ "entidad" => "Laboratoire de Pharmacologie, Hôpital de La Timone, Assistance Publique – Hôpitaux de Marseille, Marseille, France" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Service d’Hématologie, Hôpital de la Pitié-Salpêtrière, Assistance-Publique – Hôpitaux de Paris, Paris, France" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "TAGC, INSERM UMR 1090, Aix Marseille Université, Marseille, France" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento exitoso con una dosis elevada y adaptada de metotrexato en una paciente de hemodiálisis con linfoma primario del sistema nervioso central: 100 mg/m2 parece suficiente" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2558 "Ancho" => 2175 "Tamanyo" => 185663 ] ] "descripcion" => array:1 [ "en" => "Median [interquartile range] of plasma MTX concentration (μmol/L) following administration. Cycle 5 Days 15 was excluded. Small arrows represent dialysis sessions. The dashed line demarcates concentration at which folinic acid rescue was stopped. MTX: Methotrexate. MTXc: Methotrexate concentration." ] ] ] "textoCompleto" => "High-dose methotrexate (HD-MTX) is the cornerstone of the chemotherapy treatment of the primary central nervous system non-Hodgkin lymphoma (PCNSL).<a class="elsevierStyleCrossRef" href="#bib0055">1</a> Methotrexate is an antimetabolite interfering with the metabolism of folic acid, thereby blocking purine synthesis. HD-MTX defined by doses ≥500mg/m2, most often from 1 to 4g/m2, are required to cross the blood–brain barrier and achieved therapeutic level in the central nervous system.MTX is mainly excreted by the kidneys, and delayed drug clearance may lead to toxicity.<a class="elsevierStyleCrossRef" href="#bib0060">2</a> Toxicity is dependent on both duration of complete elimination from the body and serum MTX concentration (MTXc). Therapy drug monitoring is mandatory to guide folinic acid rescue and prevent severe toxicities.Because renal dysfunction conduces to delayed MTX complete elimination and critical MTXc, end-stage renal disease (ESRD) is considered as a contra-indication for HD-MTX.Nevertheless the drug is effectively cleared through hemodialysis,<a class="elsevierStyleCrossRef" href="#bib0065">3</a> and drug monitoring is easily available. However, data is missing in these particular patients.We report a case of a hemodialysis patient with PCNSL successfully treated by 100mg/m2 adjusted HD-MTX-based chemoimmunotherapy regimen.A 64-year-old woman ongoing chronic hemodialysis for 7 years for an unspecified nephropathy, presented a brutal right facial paralysis, right hemicorpus dysesthesia and balance disorders. The magnetic resonance imaging (MRI) identified a lesion affecting the brain bridge, the right middle cerebellar peduncle and cerebellar hemisphere (Supplementary Fig. 1a, b). A stereotactic biopsy confirmed the diagnosis of diffuse large B-cell lymphoma with no other location assessed by positron emission tomography (PET) scan, establishing the diagnosis of PCNSL. EBV serology was negative. After multidisciplinary discussion, accordingly to the previous published data,<a class="elsevierStyleCrossRef" href="#bib0070">4</a> the patient received 28 cycles of chemotherapy regimen R-MPV (Protocol described in Supplementary Methods). We used an adjusted the dose of MTX at 100mg/m2, based on the experience of one of the authors (unpublished).Dialysis procedures was started 24h after MTX administration and conducted daily for four hours by predilution hemodiafiltration with high-flux dialyser, dialysate flow of 500mL/min, blood flow of 250mL/min, and high dialysate bicarbonate concentration (40mmol/L). Daily dialysis was discontinued when MTXc was <0.1μmol/L.MTXc were measured before and after each dialysis session.Median MTXc 24h after infusion was 14 [9.6–15.0]μmol/L (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). No rebound phenomenon was observed. MTX was completely cleared on average at 5±0.6 days post-infusion.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Dose intensity was respected, and no course was delayed. Patient exhibited 2 episodes of undocumented sepsis with rapid favorable recovery, anemia requiring 2 red blood cells transfusion and mucositis.Intermediary evaluation after 3 cycles with MRI assessment revealed a complete response.The fifth cycle was marked by an unexplained MTX overdose at 180μmol/L 24h after administration, without clinical nor biological toxicity. The patient had an extended hemodialysis session of 16h in intensive care unit, achieving MTXc<0.5μmol/L and <0.1μmol/L after 1 more dialysis.We thus decided to stop the chemotherapy treatment after 5 cycles, given the persistent complete response on MRI (Supplementary Fig. 1c, d) and brain PET-scan.The patient is actually still in complete remission at 1 year.We report here the feasibility of HD-MTX-like therapy in hemodialysis patients, and the first use of a dose divided by more than 10 from the standard dose. Herein, with an adjusted dose at 100mg/m2, with first hemodialysis session, our patient reached the expected MTXc at H24 and treatment was well tolerated with no significant toxicity and efficient with total recovery.PCNSL is an aggressive type of lymphoma with a rapidly fatal course in the absence of treatment. HD-MTX-based chemoimmunotherapy have been shown to improve survival, even in elderly patients, and is a central part of the standard approach to treatment.<a class="elsevierStyleCrossRefs" href="#bib0060">2,4</a> Avoiding HD-MTX in hemodialysis patients leads to a loss of chance.Although its important protein-binding and low distribution volume, 63% of MTX infused can be removed after a 6h high-flux hemodialysis session, four-fold faster than renal excretion.<a class="elsevierStyleCrossRef" href="#bib0065">3</a>The strict monitoring of residual MTXc represents the major point for limiting its toxicity while keeping its effectiveness.Five cases about HD-MTX use in hemodialysis patients have been reported (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRefs" href="#bib0065">3,5–8</a> The doses used were the same as in the general population (1–4g/m2). Some authors performed daily high-flux hemodialysis 24h after MTX infusion: cMTX were then very high (>20μmol/L) after the first dialysis session,<a class="elsevierStyleCrossRefs" href="#bib0080">6–8</a> above the threshold of toxicity.<a class="elsevierStyleCrossRef" href="#bib0060">2</a> In any case, MTX was completely eliminated within 5–7 days after infusion.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Importantly, we used a dose of 100mg/m2 every 2 weeks, and cMTX were close to those described in non-ESRD patients with PCNSL treated by HD-MTX.<a class="elsevierStyleCrossRefs" href="#bib0070">4,9</a> Our patient had moderate and reversible MTX-induced toxicity, and favorable outcome. ESRD patients may also have an increased efficacy of MTX at lower doses, due to a potentially increased blood-brain barrier permeability.<a class="elsevierStyleCrossRef" href="#bib0100">10</a>We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100mg/m2 as a viable therapeutic modality in ESRD patients.Statement of ethicsThe patient gave her informed consent for the publication of this case report.Funding sourcesNone.Conflict of interestNone." "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1733779" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1529801" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1733778" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1529800" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Statement of ethics" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding sources" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 7 => array:2 [ "identificador" => "xack612050" "titulo" => "Acknowledgements" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-01-28" "fechaAceptado" => "2021-03-05" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1529801" "palabras" => array:5 [ 0 => "Methotrexate" 1 => "Central nervous system" 2 => "Lymphoma" 3 => "Hemodialysis" 4 => "Drug toxicity" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1529800" "palabras" => array:5 [ 0 => "Metotrexato" 1 => "Sistema nervioso central" 2 => "Linfoma" 3 => "Hemodiálisis" 4 => "Toxicidad farmacológica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX.We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100mg/m2, instead of the usual dose of 3500mg/m2, and daily hemodialysis started 24h later. The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment.We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100mg/m2 as a viable therapeutic modality in ESRD patients." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La quimioinmunoterapia basada en una dosis elevada de metotrexato (HD-MTX) es una parte central del enfoque terapéutico estándar del linfoma primario del sistema nervioso central (PCNSL). La insuficiencia renal causa la demora de la eliminación completa de MTX, así como la concentración crítica del mismo. A pesar de las recomendaciones, el estatus de hemodiálisis no debería excluir la HD-MTX.Reportamos el caso de una mujer de 64 años con PCNSL y tratamiento de hemodiálisis crónica que fue exitosamente tratada con quimioinmunoterapia basada en HD-MTX con una dosis ajustada de 100 mg/m2, en lugar de la dosis habitual de 3.500 mg/m2, iniciándose la hemodiálisis diaria al cabo de 24 h. La paciente no reflejó toxicidad significativa y experimentó remisión completa al cabo de un año desde la finalización del tratamiento.Nosotros argumentamos que la enfermedad renal en etapa terminal (ESRD) no constituye un escollo en absoluto para utilizar la HD-MTX para neoplasias hematológicas. Los expertos deberían considerar el uso de una dosis ajustada a 100 mg/m2 como modalidad terapéutica viable en los pacientes de ESRD." ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2558 "Ancho" => 2175 "Tamanyo" => 185663 ] ] "descripcion" => array:1 [ "en" => "Median [interquartile range] of plasma MTX concentration (μmol/L) following administration. Cycle 5 Days 15 was excluded. Small arrows represent dialysis sessions. The dashed line demarcates concentration at which folinic acid rescue was stopped. MTX: Methotrexate. MTXc: Methotrexate concentration." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "CMV: cytomegalovirus, HD: hemodialysis, HD-MTX: high dose methotrexate, PCNSL: primary central nervous system non Hodgkin lymphoma, PTLD: post-transplantation lymphoproliferative disorder, y.o.: years old." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sex and age \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Disease \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose of MTX \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type and duration of HD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Time to HD initiation after infusion (h) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MTX plasma concentration 24h after the first infusion (μmol/l) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient evolution \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Wall et al., 1996 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F13 y.o. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Osteosarcoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.2g/m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High flux6h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">150 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mutsando et al., 2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F52 y.o. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cerebral PTLD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1g/m2 and escalating dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High flux7h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pancytopenia, gastrointestinal and hepatic toxicity, invasive infection with endocarditis.Death 4 month after 2 doses treatment from a CMV related perforated gastric ulcer. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Murashima et al., 2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M58 y.o. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PCNSL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C1 3g/m2C2 6g/m2then 4g/m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High flux6h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not specified \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reshetenik et al., 2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M26 y.o. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cerebral PTLD (second line) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4g/m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High flux4h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe CMV and E.coli pneumonia requiring invasive ventilation and leading to stop chemotherapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yeung et al., 2019 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M41 y.o. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cerebral PTLD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1g/m2 and escalating dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High flux8h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical remission at 1 year after treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Previously published cases of hemodialysis patients treated by HD-MTX." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Advances and challenges in the treatment of primary central nervous system lymphoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H. 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Tratamiento exitoso con una dosis elevada y adaptada de metotrexato en una paciente de hemodiálisis con linfoma primario del sistema nervioso central: 100 mg/m2 parece suficiente

Justine Solignaca,b, Laure Farnaultc, Thomas Roberta, Raphaelle Fanciullinod, Sylvain Choquete, Philippe Bruneta,b, Geoffroy Ventonc,f, Mickaël Bobota,b,

Corresponding author

mickael.bobot@ap-hm.fr

Corresponding author.

a Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, Assistance Publique – Hôpitaux de Marseille, Marseille, France

b C2VN, INSERM, INRAE, Aix Marseille Université, Marseille, France

c Service d’Hématologie et Thérapie Cellulaire, Hôpital de la Conception, Assistance Publique – Hôpitaux de Marseille, Marseille, France

d Laboratoire de Pharmacologie, Hôpital de La Timone, Assistance Publique – Hôpitaux de Marseille, Marseille, France

e Service d’Hématologie, Hôpital de la Pitié-Salpêtrière, Assistance-Publique – Hôpitaux de Paris, Paris, France

f TAGC, INSERM UMR 1090, Aix Marseille Université, Marseille, France

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">High-dose methotrexate &#40;HD-MTX&#41; is the cornerstone of the chemotherapy treatment of the primary central nervous system non-Hodgkin lymphoma &#40;PCNSL&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Methotrexate is an antimetabolite interfering with the metabolism of folic acid&#44; thereby blocking purine synthesis&#46; HD-MTX defined by doses &#8805;500<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#44; most often from 1 to 4<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</span>&#44; are required to cross the blood&#8211;brain barrier and achieved therapeutic level in the central nervous system&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">MTX is mainly excreted by the kidneys&#44; and delayed drug clearance may lead to toxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Toxicity is dependent on both duration of complete elimination from the body and serum MTX concentration &#40;MTXc&#41;&#46; Therapy drug monitoring is mandatory to guide folinic acid rescue and prevent severe toxicities&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Because renal dysfunction conduces to delayed MTX complete elimination and critical MTXc&#44; end-stage renal disease &#40;ESRD&#41; is considered as a contra-indication for HD-MTX&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Nevertheless the drug is effectively cleared through hemodialysis&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> and drug monitoring is easily available&#46; However&#44; data is missing in these particular patients&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We report a case of a hemodialysis patient with PCNSL successfully treated by 100<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> adjusted HD-MTX-based chemoimmunotherapy regimen&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">A 64-year-old woman ongoing chronic hemodialysis for 7 years for an unspecified nephropathy&#44; presented a brutal right facial paralysis&#44; right hemicorpus dysesthesia and balance disorders&#46; The magnetic resonance imaging &#40;MRI&#41; identified a lesion affecting the brain bridge&#44; the right middle cerebellar peduncle and cerebellar hemisphere &#40;Supplementary Fig&#46; 1a&#44; b&#41;&#46; A stereotactic biopsy confirmed the diagnosis of diffuse large B-cell lymphoma with no other location assessed by positron emission tomography &#40;PET&#41; scan&#44; establishing the diagnosis of PCNSL&#46; EBV serology was negative&#46; After multidisciplinary discussion&#44; accordingly to the previous published data&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> the patient received 28 cycles of chemotherapy regimen R-MPV &#40;Protocol described in Supplementary Methods&#41;&#46; We used an adjusted the dose of MTX at 100<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#44; based on the experience of one of the authors <span class="elsevierStyleItalic">&#40;unpublished&#41;</span>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Dialysis procedures was started 24<span class="elsevierStyleHsp" style=""></span>h after MTX administration and conducted daily for four hours by predilution hemodiafiltration with high-flux dialyser&#44; dialysate flow of 500<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#44; blood flow of 250<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#44; and high dialysate bicarbonate concentration &#40;40<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41;&#46; Daily dialysis was discontinued when MTXc was &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">MTXc were measured before and after each dialysis session&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Median MTXc 24<span class="elsevierStyleHsp" style=""></span>h after infusion was 14 &#91;9&#46;6&#8211;15&#46;0&#93;<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; No rebound phenomenon was observed&#46; MTX was completely cleared on average at 5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6 days post-infusion&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Dose intensity was respected&#44; and no course was delayed&#46; Patient exhibited 2 episodes of undocumented sepsis with rapid favorable recovery&#44; anemia requiring 2 red blood cells transfusion and mucositis&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Intermediary evaluation after 3 cycles with MRI assessment revealed a complete response&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The fifth cycle was marked by an unexplained MTX overdose at 180<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L 24<span class="elsevierStyleHsp" style=""></span>h after administration&#44; without clinical nor biological toxicity&#46; The patient had an extended hemodialysis session of 16<span class="elsevierStyleHsp" style=""></span>h in intensive care unit&#44; achieving MTXc<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L and &#60;0&#46;1<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L after 1 more dialysis&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">We thus decided to stop the chemotherapy treatment after 5 cycles&#44; given the persistent complete response on MRI &#40;Supplementary Fig&#46; 1c&#44; d&#41; and brain PET-scan&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The patient is actually still in complete remission at 1 year&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We report here the feasibility of HD-MTX-like therapy in hemodialysis patients&#44; and the first use of a dose divided by more than 10 from the standard dose&#46; Herein&#44; with an adjusted dose at 100<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#44; with first hemodialysis session&#44; our patient reached the expected MTXc at H24 and treatment was well tolerated with no significant toxicity and efficient with total recovery&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">PCNSL is an aggressive type of lymphoma with a rapidly fatal course in the absence of treatment&#46; HD-MTX-based chemoimmunotherapy have been shown to improve survival&#44; even in elderly patients&#44; and is a central part of the standard approach to treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;4</span></a> Avoiding HD-MTX in hemodialysis patients leads to a loss of chance&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Although its important protein-binding and low distribution volume&#44; 63&#37; of MTX infused can be removed after a 6<span class="elsevierStyleHsp" style=""></span>h high-flux hemodialysis session&#44; four-fold faster than renal excretion&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The strict monitoring of residual MTXc represents the major point for limiting its toxicity while keeping its effectiveness&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Five cases about HD-MTX use in hemodialysis patients have been reported &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;5&#8211;8</span></a> The doses used were the same as in the general population &#40;1&#8211;4<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46; Some authors performed daily high-flux hemodialysis 24<span class="elsevierStyleHsp" style=""></span>h after MTX infusion&#58; cMTX were then very high &#40;&#62;20<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#41; after the first dialysis session&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#8211;8</span></a> above the threshold of toxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> In any case&#44; MTX was completely eliminated within 5&#8211;7 days after infusion&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Importantly&#44; we used a dose of 100<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> every 2 weeks&#44; and cMTX were close to those described in non-ESRD patients with PCNSL treated by HD-MTX&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#44;9</span></a> Our patient had moderate and reversible MTX-induced toxicity&#44; and favorable outcome&#46; ESRD patients may also have an increased efficacy of MTX at lower doses&#44; due to a potentially increased blood-brain barrier permeability&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies&#46; Experts should consider the use of adjusted dose at 100<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> as a viable therapeutic modality in ESRD patients&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Statement of ethics</span><p id="par0110" class="elsevierStylePara elsevierViewall">The patient gave her informed consent for the publication of this case report&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Funding sources</span><p id="par0115" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflict of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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          "identificador" => "sec0015"
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          "identificador" => "xack612050"
          "titulo" => "Acknowledgements"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2021-01-28"
    "fechaAceptado" => "2021-03-05"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1529801"
          "palabras" => array:5 [
            0 => "Methotrexate"
            1 => "Central nervous system"
            2 => "Lymphoma"
            3 => "Hemodialysis"
            4 => "Drug toxicity"
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        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1529800"
          "palabras" => array:5 [
            0 => "Metotrexato"
            1 => "Sistema nervioso central"
            2 => "Linfoma"
            3 => "Hemodi&#225;lisis"
            4 => "Toxicidad farmacol&#243;gica"
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">High dose methotrexate &#40;HD-MTX&#41; based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma &#40;PCNSL&#41;&#46; Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration&#46; Despite the recommendations&#44; hemodialysis status should not exclude HD-MTX&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#44; instead of the usual dose of 3500<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#44; and daily hemodialysis started 24<span class="elsevierStyleHsp" style=""></span>h later&#46; The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies&#46; Experts should consider the use of adjusted dose at 100<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> as a viable therapeutic modality in ESRD patients&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La quimioinmunoterapia basada en una dosis elevada de metotrexato &#40;HD-MTX&#41; es una parte central del enfoque terap&#233;utico est&#225;ndar del linfoma primario del sistema nervioso central &#40;PCNSL&#41;&#46; La insuficiencia renal causa la demora de la eliminaci&#243;n completa de MTX&#44; as&#237; como la concentraci&#243;n cr&#237;tica del mismo&#46; A pesar de las recomendaciones&#44; el estatus de hemodi&#225;lisis no deber&#237;a excluir la HD-MTX&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Reportamos el caso de una mujer de 64 a&#241;os con PCNSL y tratamiento de hemodi&#225;lisis cr&#243;nica que fue exitosamente tratada con quimioinmunoterapia basada en HD-MTX con una dosis ajustada de 100 mg&#47;m<span class="elsevierStyleSup">2</span>&#44; en lugar de la dosis habitual de 3&#46;500 mg&#47;m<span class="elsevierStyleSup">2</span>&#44; inici&#225;ndose la hemodi&#225;lisis diaria al cabo de 24 h&#46; La paciente no reflej&#243; toxicidad significativa y experiment&#243; remisi&#243;n completa al cabo de un a&#241;o desde la finalizaci&#243;n del tratamiento&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Nosotros argumentamos que la enfermedad renal en etapa terminal &#40;ESRD&#41; no constituye un escollo en absoluto para utilizar la HD-MTX para neoplasias hematol&#243;gicas&#46; Los expertos deber&#237;an considerar el uso de una dosis ajustada a 100 mg&#47;m<span class="elsevierStyleSup">2</span> como modalidad terap&#233;utica viable en los pacientes de ESRD&#46;</p></span>"
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        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Median &#91;interquartile range&#93; of plasma MTX concentration &#40;&#956;mol&#47;L&#41; following administration&#46; Cycle 5 Days 15 was excluded&#46; Small arrows represent dialysis sessions&#46; The dashed line demarcates concentration at which folinic acid rescue was stopped&#46; MTX&#58; Methotrexate&#46; MTXc&#58; Methotrexate concentration&#46;</p>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">CMV&#58; cytomegalovirus&#44; HD&#58; hemodialysis&#44; HD-MTX&#58; high dose methotrexate&#44; PCNSL&#58; primary central nervous system non Hodgkin lymphoma&#44; PTLD&#58; post-transplantation lymphoproliferative disorder&#44; y&#46;o&#46;&#58; years old&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sex and age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose of MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type and duration of HD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Time to HD initiation after infusion &#40;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MTX plasma concentration 24<span class="elsevierStyleHsp" style=""></span>h after the first infusion &#40;&#956;mol&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient evolution&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wall et al&#46;&#44; 1996&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">F13 y&#46;o&#46;&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">Osteosarcoma&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&#46;2<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</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">High flux6<span class="elsevierStyleHsp" style=""></span>h&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="char" 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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150&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></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mutsando et al&#46;&#44; 2012&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">F52 y&#46;o&#46;&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">Cerebral PTLD&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<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</span> and escalating dose&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">High flux7<span class="elsevierStyleHsp" style=""></span>h&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="char" 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="char" 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">Pancytopenia&#44; gastrointestinal and hepatic toxicity&#44; invasive infection with endocarditis&#46;Death 4 month after 2 doses treatment from a CMV related perforated gastric ulcer&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Murashima et al&#46;&#44; 2009&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">M58 y&#46;o&#46;&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">PCNSL&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">C1 3<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</span>C2 6<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</span>then 4<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</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">High flux6<span class="elsevierStyleHsp" style=""></span>h&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="char" 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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&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></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reshetenik et al&#46;&#44; 2015&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">M26 y&#46;o&#46;&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">Cerebral PTLD &#40;second line&#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">4<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</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">High flux4<span class="elsevierStyleHsp" style=""></span>h&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="char" 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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&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">Severe CMV and E&#46;coli pneumonia requiring invasive ventilation and leading to stop chemotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yeung et al&#46;&#44; 2019&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">M41 y&#46;o&#46;&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">Cerebral PTLD&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<span class="elsevierStyleHsp" style=""></span>g&#47;m<span class="elsevierStyleSup">2</span> and escalating dose&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">High flux8<span class="elsevierStyleHsp" style=""></span>h&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="char" 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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&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">Clinical remission at 1 year after treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Previously published cases of hemodialysis patients treated by HD-MTX&#46;</p>"
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    ]
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2009121291"
                      "Revista" => array:3 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2020"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20431041"
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        "identificador" => "xack612050"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0125" class="elsevierStylePara elsevierViewall">We thank Dr&#46; Dammar Bouchouareb&#44; Julie Bruno&#44; Mathilde Fedi &#38; Denis Bontemps for participating in the patient&#39;s care&#46;</p>"
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      ]
    ]
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    "tipo" => "SECCION"
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Article information

ISSN: 20132514
Original language: English

DOI:10.1016/j.nefroe.2022.02.007

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Year/Month	Html	Pdf	Total

2024 November	11	8	19
2024 October	87	72	159
2024 September	67	43	110
2024 August	82	111	193
2024 July	53	49	102
2024 June	60	50	110
2024 May	80	58	138
2024 April	67	46	113
2024 March	58	63	121
2024 February	65	67	132
2024 January	95	49	144
2023 December	49	31	80
2023 November	72	42	114
2023 October	39	52	91
2023 September	38	30	68
2023 August	37	22	59
2023 July	55	39	94
2023 June	102	25	127
2023 May	72	33	105
2023 April	74	41	115
2023 March	109	34	143
2023 February	63	38	101
2023 January	53	43	96
2022 December	57	47	104
2022 November	47	38	85
2022 October	98	71	169
2022 September	167	81	248
2022 August	159	69	228
2022 July	157	106	263
2022 June	107	75	182

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