NAPAAC Clinical Trials and Studies

Immunosuppressive therapy for pediatric aplastic anemia: a NAPAAC study

Abstract
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.

TransIT Study
The TransIT Study is a NAPAAC sponsored pilot study to determine whether it is feasible to identify an unrelated bone marrow donor for patients newly diagnosed with severe aplastic anemia and to treat such patients with stem cell transplant (SCT) without initial immunosuppressive therapy (IST).  Currently, patients who are diagnosed with acquired severe aplastic anemia proceed quickly to SCT if a matched family donor is identified. However, given the historical risks associated with unrelated donor SCT, the first option for severe aplastic anemia patients lacking a family donor is IST instead of transplant.  If they do not respond to IST, then most young patients will be offered transplant with an unrelated donor.  As transplant outcomes have significantly improved, physicians are questioning whether proceeding to unrelated donor SCT at the time of diagnosis- therefore avoiding both delay and risks of IST – could further improve transplant outcomes. In addition to determining whether proceeding to SCT is feasible in newly diagnosed severe aplastic anemia patients, this study will also compare the outcomes of the patients treated with these two different approaches:  standard immunosuppressive therapy versus unrelated donor bone marrow transplantation.