title: 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, post-transplantation 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 CD20+ 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 + B lymphoid malignancies are warranted.
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, Hospital for Sick Children, Ontario, Toronto, Canada.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ceppi
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, Hospital for Sick Children, Ontario, Toronto, Canada.
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital and Justus-Liebig-University, Giessen, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Woessmann
authors.affiliation: Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Davies
authors.affiliation: Department of Pediatric Hematology/Oncology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Lassaletta
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical University of Vienna, St. Anna Children's Hospital, Vienna, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Reismüller
authors.affiliation: Department of Paediatrics, Institution for Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Mellgren
authors.affiliation: Department of Pediatric Hemato-Oncology, University Hospitals of Leuven, Leuven, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Uyttebroeck
authors.affiliation: Pediatric Service, Portuguese Institute of Oncology, Porto, Portugal.
authors.forename: Iris
authors.initials: I
authors.lastname: Maia
authors.affiliation: Pediatric Oncology, King Abdulaziz Medical City - National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Shaker
authors.initials: S
authors.lastname: Abdullah
authors.affiliation: Department of Hematology/Oncology, Federal Center for Pediatric Hematology, Oncology and Immunology Named by D. Rogachev, Moscow, Russia.
authors.forename: Natasha
authors.initials: N
authors.lastname: Miakova
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, University of Hawai'I John a. Burns School of Medicine, Honolulu, Hawai'i.
authors.forename: Darryl
authors.initials: D
authors.lastname: Glaser
authors.affiliation: Kids Cancer Centre, Sydney Children's Hospital and School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Cohn
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, Hospital for Sick Children, Ontario, Toronto, Canada.
authors.forename: Oussama
authors.initials: O
authors.lastname: Abla
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical University of Vienna, St. Anna Children's Hospital, Vienna, Austria.
authors.forename: Andishe
authors.initials: A
authors.lastname: Attarbaschi
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, Hospital for Sick Children, Ontario, Toronto, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Alexander
mesh_terms: D000293:Adolescent; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004341:Drug Evaluation; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007223:Infant; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D008297:Male; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011183:Postoperative Complications / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D012074:Remission Induction; D012189:Retrospective Studies; D000069283:Rituximab / Q000008:administration & dosage* / Q000009:adverse effects; D016879:Salvage Therapy; D012640:Seizures / Q000139:chemically induced; D014180:Transplantation; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000069283:Rituximab