Safety, efficacy, and immune reconstitution after rituximab therapy in pediatric patients with chronic or refractory hematologic autoimmune cytopenias. Pediatr Blood Cancer 2008 Apr;50(4):822-5
Date
06/16/2007Pubmed ID
17570702DOI
10.1002/pbc.21264Scopus ID
2-s2.0-40449106057 (requires institutional sign-in at Scopus site) 87 CitationsAbstract
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 x 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.
Author List
Rao A, Kelly M, Musselman M, Ramadas J, Wilson D, Grossman W, Shenoy SMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Antibodies, Monoclonal
Antibodies, Monoclonal, Murine-Derived
Antineoplastic Agents
Autoimmune Diseases
B-Lymphocytes
Cell Count
Child
Child, Preschool
Dose-Response Relationship, Drug
Female
Hematologic Diseases
Humans
Immunoglobulin A
Immunoglobulin G
Immunoglobulin M
Male
Recurrence
Rituximab
