Incidence and outcomes of subsequent malignancy after allogeneic hematopoietic stem cell transplantation in adult patients with severe aplastic anemia.

Purpose: This study investigated the occurrence of subsequent malignancies (SM) in adult patients with severe aplastic anemia (SAA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to address the lack of large-scale, long-term data on this complication.

Methods: A retrospective cohort analysis of 376 adult patients with SAA who underwent allo-HSCT between 2002 and 2021 at a single center was conducted. The incidence, risk factors, and survival impact of SM were also examined.

Results: During the follow-up period, 31 cases of SM (8.2%) were identified. Approximately one-third (32.3%) of SM cases were hematologic malignancies, including post-transplant lymphoproliferative disorder (16.1%), myelodysplastic neoplasm (6.5%), and acute myeloid leukemia (3.2%). Solid tumors accounted for 67.7% of cases, with thyroid cancer being the most prevalent (25.8%). The 15-year cumulative incidence of SM was 11.2%, and the hazard ratio for overall survival according to the development of SM was 16.25 (p < 0.001). High-dose total body irradiation (TBI), anti-thymocyte globulin (ATG), and moderate-to-severe chronic graft-versus-host disease (GVHD) were identified as significant risk factors for subsequent malignancy. Post-transplant SAA patients exhibited a 3.54-fold higher observed cancer incidence than the expected incidence calculated from the age-, sex-, and calendar year-matched general population.

Conclusion: SM is a significant long-term complication in patients with posttransplant SAA and has a substantial survival impact. Patients receiving high-dose TBI or ATG, and those with moderate-to-severe chronic GVHD, require vigilant long-term monitoring.