Therapy-related myeloid neoplasms (t-MNs) are a late complication of cytotoxic therapy and are defined as a distinct entity by the World Health Organization. Although the link between chemotherapy exposure and risk of subsequent t-MN is well described, the association between radiation monotherapy (RT) and t-MN risk is less definitive. We analyzed 109 consecutive patients who developed t-MNs after RT and describe latencies, cytogenetic profile, mutation analyses, and clinical outcomes. The most common cytogenetic abnormality was a clonal abnormality in chromosome 5 and/or 7, which was present in 45% of patients. The median latency from RT to t-MN diagnosis was 6.5 years, with the shortest latency in patients with balanced translocations. One-year overall survival (OS) was 52% and 5-year OS was 22% for the entire cohort. Patients with chromosome 5 and/or 7 abnormalities experienced worse 1-year OS (37%) and 5-year OS (2%) compared with other cytogenetic groups (P < .0001). Sixteen patients underwent net-generation sequencing; ASXL1 and TET2 were the most commonly mutated genes (n = 4). In addition, 17 patients underwent germline variant testing and 3 carried pathogenic or likely pathogenic germline variants. In conclusion, patients with t-MN after RT monotherapy have increased frequencies of chromosome 5 and/or 7 abnormalities, which are associated with poor OS. In addition, pathogenic germline variants may be common in patients with t-MN after RT monotherapy.
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