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Although measurable residual disease (MRD) status via optimal quantitative polymerase chain reaction (qPCR) response (OPR; qPCR &amp;lt;0.1% at the end of induction and &amp;lt;0.01% during\/after consolidation) of fusion transcripts predicts survival, the impact of baseline myeloid mutations on OPR and survival with FLAG remains uncertain. We interrogated these factors in 219 first-line patients with CBF-AML (median age 52 years; range, 19\u201380) treated on a phase II trial (NCT00801489); 51% received FLAG-GO and 49% FLAG idarubicin. Baseline mutations included 49% kinase pathways (non-MAP kinase), 44% MAP kinase, 11% DNMT3A\u2013ASXL1\u2013TET2, and 7% transcription factors. Five-year relapse-free survival and OS were 67% and 74% overall, respectively, 77% and 80% with FLAG-GO. On multivariate analysis, baseline mutations did not affect OPR or survival, whereas FLAG-GO favored both. In CBF-AML, FLAG-based therapy possibly attenuates the prognostic impact of concurrent baseline genomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>In CBF-AML treated with conventional intensive chemotherapy, usually 7 + 3, baseline mutations in KIT, chromatin modulators, cohesin complex, etc., garner suboptimal MRD clearance and survival. In our analysis, FLAG-based therapy abrogated the impact of baseline mutations on OPR and survival in CBF-AML, while showing promising long-term survival using FLAG-GO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2643-3230.bcd-25-0477","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T14:17:15Z","timestamp":1776176235000},"page":"572-585","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrated Analysis of Genomics, Molecular Responses, and Outcomes of CBF-AML with FLAG-Based Therapy on a Phase II Trial"],"prefix":"10.1158","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6831-2567","authenticated-orcid":false,"given":"Jayastu","family":"Senapati","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Texas MD Anderson Cancer Center 1 Department of 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