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.