Intrathecal therapy with rituximab in central nervous system involvement of post-transplant lymphoproliferative disorder

Abstract

Post-transplant lymphoproliferative disorder (PTLD) caused by Epstein-Barr virus (EBV) is a severe complication in high-risk allogeneic hematopoietic stem cell transplant (HSCT) recipients. Central nervous system (CNS) involvement of PTLD is a very rare event in patients with HSCT. As no established standard therapy in CNS-EBV-PTLD is available, the aim of this study was analysis of the safety and efficacy of intrathecal rituximab therapy in a group of eight children and adolescents with CNS-EBV-PTLD. Seven patients responded to therapy: all clinical symptoms and EBV-DNA viral load resolved after a median 2 (range: 1-7) doses of rituximab. However, some magnetic resonance imaging (MRI) changes in brain scan persisted in two patients. In all patients, except one, no adverse events of the therapy were observed. In conclusion, intrathecal rituximab administration seems to be an effective and safe method of treatment of CNS-EBV-PTLD in pediatric stem cell recipients. We recommend this treatment modality for further investigation.

Intrathecal rituximab for EBV-associated post-transplant lymphoproliferative disorder with central nervous system involvement unresponsive to intravenous rituximab-based treatments: a prospective study

“…5,6,12 Unfortunately, IV rituximab is poorly effective against CNS-PTLD because of low penetrance across the blood-brain barrier. [13][14][15] In this study, only 3 of 14 patients were responsive to the IV rituximab-based treatments, which was consistent with the reports. 6,7 Recently, a few studies demonstrated that intrathecal administration of rituximab was an effective and safe method for pediatric CNS-PTLD.…”

“…6,7 Recently, a few studies demonstrated that intrathecal administration of rituximab was an effective and safe method for pediatric CNS-PTLD. 7, 14 Czyzewski, et al 14 reported that seven of eight children with CNS-PTLD were responsive to intrathecal rituximab. Letter to the Editor Bonney et al 7 documented successful management of intrathecal rituximab in two pediatric primitive CNS-PTLD following the failure of IV rituximab.…”

Safety and efficacy of intrathecal rituximab in children with B cell lymphoid CD20+ malignancies: An international retrospective study

“…Rituximab administration was well tolerated in their heavily pretreated study group, with no clinical evidence of neurotoxicity after a 24-month follow-up period. Czyzewski et al [9] published a study describing intrathecal rituximab therapy in a group of eight children and adolescentswith CNS-EBV-PTLD. Only one patient had a short episode of seizures observed after the third intrathecal rituximab infusion.…”

“…After intravenous administration of rituximab CSF concentration remains very low, ranging from 0.1 to 0.2% of systemic rituximab concentration [23]. Results in patients with B cell lymphoid malignancies with leptomeningeal infiltration suggest that IT or intraventricular rituximab may have a therapeutic effect [9,[24][25][26][27][28][29]. IT or intraventricular administration of rituximab could be a useful addition to therapy of patients with B-cell malignancies involving the CNS and possibly also could be considered for prophylaxis for malignancies with risks of CNS recurrence.…”

“…IT or intraventricular administration of rituximab could be a useful addition to therapy of patients with B-cell malignancies involving the CNS and possibly also could be considered for prophylaxis for malignancies with risks of CNS recurrence. However, clinical experience with this route of administration is very limited, especially in children [9,28,29] Table I.…”