Therapy-related myeloid neoplasms with different latencies: a detailed clinicopathologic analysis

Therapy-related myeloid neoplasm (t-MN) arising in patients with prior cytotoxic treatments is considered a distinct entity due to its unfavorable prognosis. Latencies between the initial cytotoxic therapy and the occurrence of t-MNs vary but usually fall between 1 and 10 years. t-MNs with unusually short or long latencies are not well characterized. It is unclear if they are biologically similar to the ones with ordinary latencies and should be kept in the t-MN entity. We compiled a cohort of t-MN cases including short (<1 year), ordinary (1-10 years), and extended (>10 years) latencies from two tertiary medical centers. Both the t-MNs with ordinary and extended latencies showed high likelihood of high-risk genetic abnormalities and demonstrated no significant survival differences. But the t-MNs with extended latencies were more likely associated with history of multiple cancers (p = 0.007) and were younger at the time of cytotoxic treatments (p < 0.001) when compared to the t-MNs with ordinary latencies. The t-MN with short latencies appears to be a very rare and highly heterogeneous group. In summary, the genetic composition appears similar in the t-MNs with ordinary and extended latencies. However, the association between the t-MN with extended latencies and history of multiple cancers raises a possibility that cancer predisposition may contribute to the accumulation of genetic abnormalities in these patients. Investigation into potential germline mutations in the t-MN patients with extended latencies may provide important information for related family members.