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Safety, efficacy, and immune reconstitution after rituximab therapy in pediatric patients with chronic or refractory hematologic autoimmune cytopenias
Author(s) -
Rao Aarati,
Kelly Michael,
Musselman Mark,
Ramadas Jagadeesh,
Wilson David,
Grossman William,
Shenoy Shalini
Publication year - 2008
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.21264
Subject(s) - medicine , rituximab , neutropenia , refractory (planetary science) , evans syndrome , gastroenterology , immunology , anemia , pediatrics , autoimmune hemolytic anemia , chemotherapy , lymphoma , physics , astrobiology
Background Autoimmune hematologic cytopenias in children often require therapeutic intervention. We report a prospective pediatric multicenter trial of rituximab for refractory or steroid‐dependent patients. Methods Four doses of rituximab (375 mg/m 2 /dose) were administered weekly. Patients without response after three doses were offered dose escalation to 750 mg/m 2 /dose/week × 3. Safety, efficacy, and immunologic tests were evaluated after therapy. Results Twenty‐nine of 30 children (2–18 years) with thrombocytopenia (21), hemolytic anemia (6), Evans syndrome (2), and neutropenia (1) received at least four doses of rituximab. One developed anaphylaxis with the first dose. One patient was subsequently diagnosed with monosomy 7 myelodysplasia. Of 28 remaining patients, 9 received dose escalation. Responders discontinued other therapy following rituximab. The overall response rate was 72% with median follow‐up of 18 months. Complete remission was observed in 14 (50%); all received four doses of rituximab. Partial remission (PR) was observed in six (22%); five had received dose escalation. Of four relapses, 4–24 months after therapy, two were retreated with rituximab and achieved second remission. No major infections were encountered. Circulating B‐cells were depleted by 1 month and normalized by 1 year. IgM, Ig A, and IgG levels decreased 6, 9, and 12 months after therapy, respectively, but remained near normal range. Tetanus toxoid antibody titers remained detectable. Conclusions Rituximab was well tolerated, and induced sustained remissions in children with refractory immune cytopenias. Dose escalation and re‐treatment after relapse elicited additional responses. Rituximab therapy should be considered prior to potential interventions with higher toxicity. Pediatr Blood Cancer 2008;50:822–825. © 2007 Wiley‐Liss, Inc.