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

Abstract

Central nervous system (CNS) involvement in patients with mature B non-Hodgkin lymphoma, posttransplantation proliferative disorder and acute lymphoblastic leukemia confers a significantly inferior prognosis as compared to patients without CNS disease. Intrathecal (IT) or intraventricular administration of rituximab is an option for this group of patients. We report 25 children with CNS involvement of CD201 B lymphoid malignancies who received in total 163 IT/intraventricular rituximab doses. The median number of doses received by each patient was 6, with a median dose of 25 mg. The most common adverse events were Grades 1 and 2 peripheral neuropathies in five patients (20%), allergy in two patients, and headache in two patients. These events were self-limited, occurring in the 48 hours after treatment and resolving within 24 hr. Three patients presented with more severe though transient side effects, one with a Grade III neuropathy and two with seizure. Eighteen patients (72%) of those treated with IT/intraventricular rituximab, with or without other CNS directed treatment, achieved a CNS remission. This case series suggests that IT/ intraventricular rituximab has therapeutic efficacy and relatively limited toxicity. Prospective trials of IT/ intraventricular rituximab for patients with CNS involvement of CD20 1 B lymphoid malignancies are warranted.

Involvement of the central nervous system in acute lymphoblastic leukemia: opinions on molecular mechanisms and clinical implications based on recent data

“…Limited efficacy in the CNS is probably due to their poor penetration into the CNS which can, however, be overcome by intrathecal or intraventricular application [95,96]. Indeed, treatment of pediatric CD20positive B cell lymphoid malignancies including relapsed ALL via intrathecal injection of rituximab resulted in complete CNS remission in the majority of patients, with an acceptable toxicity profile in small-sized clinical studies [97,98]. Further approaches for antibody-based immunotherapy are on the way.…”

Prolonged Survival of Acute Lymphoblastic Leukemia with Intrathecal Treatments for Isolated Central Nervous System Relapse

“…However, these patients received prior spinal or cranial irradiation and were significantly younger (none older than age 21) than our patient [ 17 ]. More recently, a case series of pediatric patients with B-cell lymphoid CD20+ malignancies reported an ongoing complete remission in only one of three patients with acute lymphoblastic leukemia who were treated with intraventricular or intrathecal rituximab [ 18 ]. Thus, preliminary data on the use of intrathecal or intraventricular rituximab therapy for CNS involvement of CD20+ acute lymphoblastic leukemia suggest a potential benefit, but requires further evaluation in this setting.…”

Characteristics and outcomes of non-Hodgkin’s lymphoma patients with leptomeningeal metastases

“…Four commonly used drugs are liposomal Ara-C, Ara-C, MTX and thiotepa, all of which result in similar OS. In our center, we customarily utilize MTX and Ara-C. Clinical trials of new intra-CSF agents such as rituximab for the treatment of CD20-positive B-cell lymphoma are being performed, and the results [18–20] suggest that rituximab is feasible and highly effective for IT treatment. A large-scale prospective clinical trial of IT rituximab is needed to further promote clinical application of this therapy.…”