Safety, efficacy, and immune reconstitution after rituximab therapy in pediatric patients with chronic or refractory hematologic autoimmune cytopenias.
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.
Rao
Aarati
A
Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA.
Kelly
Michael
M
Musselman
Mark
M
Ramadas
Jagadeesh
J
Wilson
David
D
Grossman
William
W
Shenoy
Shalini
S
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006402:Hematologic Diseases / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D012008:Recurrence; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D000069283:Rituximab