Bone Marrow Failure Disorders

Clonal evolution and development of secondary myeloid malignancy are concerning potential long-term complications of immunosuppressive treatment for immune aplastic anemia (AA). In a retrospective cohort study (abstract 601) presented at the 63rd Annual Annual Meeting of the American Society of Hematology (ASH), researchers from the National Heart, Lung, and Blood Institute investigated predictor factors, genetic characteristics, and long-term outcomes of 659 patients with severe AA. Following immunosuppression, 95 patients developed clonal evolution — either secondary myeloid neoplasia (categorized as "high-risk"; n=59) or isolated chromosomal abnormalities without morphologic dysplasia ("low-risk"; n=36). Overall survival at 5 years in patients with high-risk evolution was 35%, compared with 84% of those with low-risk evolution (P <.001). OS was higher for patients with high-risk evolution who underwent hematopoietic stem cell transplant (HSCT; n=26) compared with chemotherapy or supportive care (P =.005). Because MDS-associated genetic mutations, particularly RUNX1, were enriched in high-risk evolution, the authors concluded that "further study of the role of RUNX1 in high-risk clonal evolvers may give insight into leukemogenesis in AA."