Presentation and Outcomes of Severe Aplastic Anemia
Immunosuppression leads to remission in most children with idiopathic severe aplastic anemia (SAA). However, over the long term, some patients may relapse, develop other bone marrow problems, or experience unexpected therapy-related side effects. Furthermore, immunosuppressive protocols and supportive care standards differ between institutions, and it is not clear which therapeutic approach is optimal. Last, occasionally a child diagnosed with SAA may, instead, have an unrecognized inherited bone marrow failure syndrome that requires very different clinical management.
We are reviewing the medical records of over 300 children with severe aplastic anemia treated at NAPAAC-member institutions across North America during the last decade. Through this study, we hope to better understand what determines risk of relapse and therapy-related complications in children with SAA and determine whether differences in immunosuppressive protocols and supportive care affect outcome. A companion study will provide a central review of diagnostic bone marrow aspirates and biopsies to identify potential diagnostic challenges. This work will help establish a consensus diagnostic and therapeutic approach to children with severe aplastic anemia, and fuel future hypothesis-driven studies on this challenging disease.
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.