Clinical and Genetic Profiles and Outcomes of Allogeneic HSCT in Secondary Myelodysplastic Syndrome Following Aplastic Anemia

Aplastic anemia (AA) often complicates due to clonal diseases like secondary myelodysplastic syndrome (sMDS). We retrospectively analyzed 25 sMDS patients post-AA, 337 patients with de novo MDS, and 285 AA patients without MDS progression who received allogeneic hematopoietic stem cell transplantation (allo-HSCT), both before and after propensity score matching. Among sMDS patients, 80% had prior non-severe AA. Their median age at HSCT was 35 years, between de novo MDS (45 years, P=0.021) and non-progressing AA patients (24 years, P<0.001). Compared to de novo MDS, sMDS patients had lower pre-transplant platelet counts and frequently presented with early MDS status (2016 criteria: 44.0% vs 24.6%, P=0.033; 2022 criteria: 48.0% vs 21.4%, P=0.002). They exhibited higher rates of GATA2, PIGA mutations, and -7/del(7q) loss, while U2AF1 mutations were more common in de novo MDS. In sMDS, -7/del(7q) was often the sole chromosomal abnormality, significantly affecting the 1-year relapse incidence (25.0% vs 0.0%, P=0.045). Adjusted for baseline characteristics, sMDS survival was marginally better than de novo MDS. When AA severity was balanced, survival between sMDS and non-progressing AA showed no significant difference. Overall, post-AA sMDS patients exhibited unique clinical and genetic profiles, with -7/del(7q) holding distinctive significance, and allo-HSCT proved effective for these patients.