Impact of primary cancer history and molecular landscape in therapy-related myeloid neoplasms.

Background: Therapy-related myeloid neoplasms (t-MN) are aggressive hematologic malignancies with poor prognosis and high-risk clinical features. Recent advances have highlighted the role of molecular data in refining prognostic models. This study aims to analyze a monocentric cohort of t-MN patients, focusing on the clinical and prognostic impact of prior malignancies and their associated molecular landscape. Methods: A retrospective analysis was conducted on 61 patients diagnosed with t-MN from an Oncology Hospital and referred to a hematology Unit. Diagnoses were based on established criteria for therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML), with a history of prior exposure to cytotoxic therapy. Cytogenetic and molecular analyses supported the diagnoses. Risk stratification was performed using the revised International Prognostic Scoring System (IPSS-R) and molecular IPSS (IPSS-M) for t-MDS and the 2022 European LeukemiaNet (ELN) classification for t-AML. Results: Overall, 61 patients with t-MN were diagnosed: 38 (62.3%) with t-MDS, and 23 (37.7%) with t-AML. The median latency from primary cancer to t-MN diagnosis was 5.8 years (IQR: 2.6-12.5). Risk stratification identified 63.2% of t-MDS cases as IPSS-R very-low to intermediate risk, while 57.9% were reclassified as IPSS-M moderate-high to very high risk. Patients with prior hematologic cancer showed a greater tendency toward higher IPSS-R ( Conclusions: t-MN exhibits distinct clinical and molecular profiles according to prior malignancy type. Intriguingly, our analysis reveals a distinct latency pattern in