{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:11:57Z","timestamp":1792012317845,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Patients with newly diagnosed acute myeloid leukemia (ND\u2010AML) derive variable survival benefit from venetoclax\u2009+\u2009hypomethylating agent (Ven\u2010HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND\u2010AML patients treated with Ven\u2010HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR)\u00a0or without (CRi) count recovery. Multivariable analysis\u2013derived hazard ratios (HR), including 1.8 for European LeukemiaNet (ELN) adverse karyotype, 4.7 for\n KMT2Ar<\/jats:italic>\n , 1.7 for\n TP53<\/jats:italic>\n MUT<\/jats:sup>\n , 2.6 for\n KRAS<\/jats:italic>\n MUT<\/jats:sup>\n , and 2.1 for\n IDH2<\/jats:italic>\n WT<\/jats:sup>\n were applied to develop an HR\u2010weighted risk model: low, intermediate, and high; respective median survival censored for allogeneic stem\u00a0cell transplant\u00a0(ASCT) (3\u2010year survival) were \u201cnot reached\u201d (67%), 19.1 (33%), and 7.1\u2009months (0%). In patients achieving CR\/CRi, adverse karyotype,\n KMT2Ar<\/jats:italic>\n ,\n KRAS<\/jats:italic>\n MUT<\/jats:sup>\n ,\n IDH2<\/jats:italic>\n WT<\/jats:sup>\n predicted inferior survival, allowing for a complementary response\u2010stratified risk model. The model was externally validated and was shown to be superior to the ELN 2024 risk model (AIC 179 vs. 195 and AUC 0.77 vs. 0.69). Survival was inferior with failure to achieve CR\/CRi or not receiving ASCT; 3\u2010year survival for high\u2010risk with or without ASCT was 42% versus 0% (\n p<\/jats:italic>\n \u2009<\u20090.01); intermediate 72% versus 43% (\n p<\/jats:italic>\n \u2009=\u20090.06); and low\u2010risk 88% versus 78% (\n p<\/jats:italic>\n \u2009=\u20090.53). The Mayo genetic risk models offer pre\u2010treatment and response\u2010based prognostic tools for ND\u2010AML treated with Ven\u2010HMA. The current study underscores the prognostically indispensable role of achieving CR\/CRi and ASCT.\n <\/jats:p>","DOI":"10.1002\/ajh.27564","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T11:53:56Z","timestamp":1734090836000},"page":"260-271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Mayo Genetic Risk Models for Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax\u2009+\u2009Hypomethylating Agent"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9104-6172","authenticated-orcid":false,"given":"Naseema","family":"Gangat","sequence":"first","affiliation":[{"name":"Division of Hematology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azeem","family":"Elbeih","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic Rochester Minnesota 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