Older Age and Complex Karyotype Are the Main Predictors of Mortality Irrespective of Transplantation in Therapy‐Related Myeloid Neoplasms

Therapy‐related myeloid neoplasms (t‐MN) are late complications of cancer therapies. We retrospectively analyzed 86 adults diagnosed from 2007 to 2025 with t‐MN (acute myeloid leukemia [AML] n = 31, myelodysplastic neoplasms [MDS] n = 38, MDS/AML n = 17). We estimated overall survival (OS) and cumulative incidence of disease related mortality (DRM). Uni‐ and multivariable models identified predictors of mortality; interaction models defined the role of allogeneic hemopoietic stem cell transplantation (allo‐HSCT) in elderly patients and complex karyotype (CK) t‐MN. Median age at diagnosis was 65.5 years, previous cancer was solid in 29% or hematologic in 71%. Among 66/86 candidates to active therapy, 39/66 were candidates to allo‐HSCT and 24 received it. In our cohort, we had demonstrated a high prevalence of adverse baseline genomics (47% of CK) and poor OS (11.94 months), partially mitigated by allo‐HSCT (29.47 vs. 9.01 months, p = 0.028). In univariable and multivariable analysis, age ≥ 65 years and CK but not allo‐HSCT were DRM predictors. In interaction models, age ≥ 65 years remained deleterious regardless of transplant whereas allo‐HSCT could offset CK‐related risk, supporting transplantation even in high‐risk cytogenetics, when disease control and fitness criteria are met. Overall, t‐MN remained highly lethal, with DRM primarily driven by age and CK; allo‐HSCT attenuated cytogenetic risk.