OBJECTIVES. Our goal was to determine long-term efficacy and safety of B-cell–depletion therapy for children with autoimmune thrombocytopenia and autoimmune hemolytic anemia in pediatric systemic lupus erythematosus.
PATIENTS AND METHODS. A retrospective, single-center cohort study was conducted including all patients with pediatric systemic lupus erythematosus who were diagnosed with autoimmune thrombocytopenia and/or autoimmune hemolytic anemia and treated with rituximab. Treatment efficacy and safety parameters were monitored and recorded.
RESULTS. Nine patients with pediatric systemic lupus erythematosus were included in the study: 5 had autoimmune thrombocytopenia, 3 had autoimmune hemolytic anemia, and 1 had both. There were 5 female and 4 male patients; median age at diagnosis of pediatric systemic lupus erythematosus was 14 years (range: 8–16 years); and median pediatric systemic lupus erythematosus disease duration to time of rituximab treatment was 6 months (range: 2–30 months). Complete response was achieved in all 6 children with autoimmune thrombocytopenia (median time to complete response: 2 weeks [range: 1–12 weeks]). Two patients' conditions flared at 48 and 68 weeks, respectively, and were re-treated. The remaining 4 patients continued to be in remission at 24, 32, 36, and 88 weeks, respectively. All 4 children with autoimmune hemolytic anemia achieved complete response at a median time of 4 weeks (range: 4–32 weeks). All patients remained in complete response at 24, 44, 84, and 100 weeks of follow-up. Complete B-cell depletion was seen in all children after rituximab treatment. No serious infections occurred, but 1 patient had an infusion reaction.
CONCLUSIONS. Preliminary evidence suggests that B-cell–depletion therapy with rituximab is an efficacious and safe treatment for autoimmune thrombocytopenia and autoimmune hemolytic anemia in pediatric systemic lupus erythematosus. Despite the prolonged effect on B-cell numbers and function, no serious infections were observed.
Comments
Serious Infections and "Iatrogenic Immunodeficiency in a Patient treated with Rituximab
In the January 2009 edition of Pediatrics, Kumar et al1 describe the safety and efficacy of rituximab for the treatment of autoimmune thrombocytopenia and autoimmune hemolytic anemia (AIHA) in pediatric systemic lupus erythematosus (SLE). Despite the fact that all patients experienced “complete B cell depletion” for four to seven months, the authors reported no serious infections and suggest that routine intravenous gamma globulin (IVIg) may not be required for these patients. We would like to report a child who suffered from recurrent serious infections for five months after receipt of a single dose of rituximab.
The patient was a 20 month-old female with AIHA who received one dose of rituximab (375 mg/m2) at seventeen months of age when her hemoglobin decreased to 5.4 g/dL despite oral corticosteroid therapy. Although her anemia resolved 2 weeks later, she subsequently required 6 separate hospital admissions for pneumonia, sinusitis, and periorbital cellulitis. An immune evaluation demonstrated lymphopenia (absolute lymphocyte count of 960 cells/mm3), complete B lymphocyte depletion (CD19+ cells of 0 cells/mm3), and hypogammaglobulinemia (IgG of 117 mg/dL). She was started on monthly IVIg (400 mg/kg) and her corticosteroid dose was tapered. Her B-lymphocyte count normalized seven months after rituximab was given, at which time her anemia recurred. Corticosteroid therapy was re-started with successful recovery of her hemoglobin concentration. She continues to receive replacement immunoglobulin therapy and remains healthy.
Rituximab administration results in rapid and often prolonged depletion of CD20+ B cells2,3,4. While the use of rituximab for various hematological disorders shows promise, the risk of potential long-term immunosuppression must be considered, especially in the context of concomitant prolonged corticosteroid therapy or use of other immunosuppressive agents.
We suggest a routine baseline screen of humoral immunity with quantitative analysis of serum IgG, IgA, IgM and B-lymphocyte numbers identified by CD19 and/or CD20 prior to rituximab administration in children. Following rituximab administration, IgG levels and B-lymphocyte numbers should be monitored over time, especially in those patients developing recurrent infections, failure to thrive, or other clinical manifestations of secondary, iatrogenic immunodeficiency. Such measures may identify patients with underlying humoral immunodeficiency in whom rituximab therapy may be contraindicated, and also identify candidates for IVIg replacement therapy.
REFERENCES 1. S Kumar, S Benseler, Melanie Kirby-Allen, and Earl D. Silverman. B-Cell Depletion for Autoimmune Thrombocytopenia and Autoimmune Hemolytic Anemia in Pediatric Systemic Lupus Erythematosus. Pediatrics 2009; 123: e159- e163. 2. A Rao, M Kelly, M Musselman, J Ramada et al. Safety, Efficacy, and Immune Reconstitution After Rituximab Therapy in Pediatric Patients with Chronic or Refractory Hematologic Autoimmune Cytopenias. Pediatr Blood Cancer 2008; 50: 822–825. 3. M El-Hallak, B Binstadt, A Leichtner et al. Clinical Effects and Safety of Rituximab for Treatment of Refractory Pediatric Autoimmune Diseases. J Pediatr 2007;150: 376-82. 4. P Quartier, B Brethon, P Philippet et al. Treatment of childhood autoimmune haemolytic anaemia with rituximab. The Lancet 2001; 358: 1511- 1513.
Conflict of Interest:
None declared