| Summary: | ABSTRACTAcute myeloid leukemia (AML) that develops along with prior or concurrent tumors without previous cyto- or radiotherapy (pc-AML) is an essential subset of AML but is often ignored and ambiguous. The biological and genetic characteristics of pc-AML remain largely unknown. Moreover, it is unclear whether pc-AML should be treated as de novo or secondary AML, whereas most clinical trials exclude it due to comorbidities. We performed a retrospective study of 50 patients with multiple neoplasms over five years. We focused on characteristics, treatment regimens, response rate, and prognosis of pc-AML, compared with therapy-related AML (tAML) and AHD-AML (AML discovered following prior hematologic disorders) as controls. We report the first detailed distribution of secondary tumors associated with hematological disorders. The incidence of pc-AML was 30% of all multiple neoplasms, and it was predominantly found in male and older participants. Nearly three-quarters of gene mutations affected epigenetic regulation and signaling pathways, and NPM1, ZRSR2, and GATA2 occurred exclusively in pc-AML. No significant differences were in CR, and pc-AML had an inferior OS similar to that of tAML and AHD-AML. More patients received hypomethylation agents (HMAs) in combination with venetoclax (HMAs + VEN) than intensive chemotherapy (IC) (65.7% vs 31.4%), and there was a trend toward improved OS in HMAs + VEN-based than in IC-based patients, whose 2-year estimated OS times were 53.6% and 35.0%, respectively. In conclusion, our results collectively support pc-AML as a biologically and genetically distinct entity with high-risk and dismal outcomes, and HMAs in combination with venetoclax-based regimens may benefit patients with pc-AML.
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