Quality of response to immunosuppressive therapy and long-term outcomes for pediatric severe aplastic anemia remain incompletely characterized. Contemporary evidence to inform treatment of relapsed or refractory severe aplastic anemia are also limited for pediatric patients. The clinical features and outcomes for 314 children treated from 2002-2014 with immunosuppressive therapy for acquired severe aplastic anemia were analyzed retrospectively from 25 institutions in the North American Pediatric Aplastic Anemia Consortium. The majority of subjects (n=264) received horse anti-thymocyte globulin plus cyclosporine with 61 months median follow up. Following horse anti-thymocyte globulin/cyclosporine, 71.2% (95% CI: 65.3,76.6) achieved an objective response. In contrast to adult studies, the quality of response attained in pediatric patients was high, with 59.8% (95% CI: 53.7,65.8) reaching a complete response and 68.2% (95% CI: 62.2,73.8) attaining at least a very good partial response with a platelet count ≥50,000/μL. At 5 years post-horse anti-thymocyte globulin/cyclosporine, overall survival was 93% (95% CI: 89,96), but event free survival without subsequent treatment was only 64% (95% CI: 57,69) without a plateau. Twelve of 171 evaluable patients (7%) acquired clonal abnormalities after diagnosis with a median time of 25.2 months (range 4.3-71 months) post-treatment. Myelodysplastic syndrome or leukemia developed in 6/314 (1.9%). For relapsed/refractory disease, treatment with a hematopoietic stem cell transplant had a superior event-free survival compared to second immunosuppressive therapy treatment in a multivariate analysis (HR=0.19, 95% CI:0.08, 0.47, p=0.0003). This study highlights the need for improved therapies leading to sustained high quality remission for children with severe aplastic anemia.
