{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T15:37:09Z","timestamp":1793720229162,"version":"4.6.1"},"reference-count":58,"publisher":"American Society of Hematology","issue":"19","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Somatic mutations in isocitrate dehydrogenase (IDH) genes occur frequently in adult acute myeloid leukemia (AML) and less commonly in pediatric AML. The objective of this study was to describe the prevalence, mutational profile, and prognostic significance of\u00a0IDH\u00a0mutations in AML across age. Our cohort included 3141 patients aged between &amp;lt;1 month and 88 years treated on Children\u2019s Cancer Group\/Children\u2019s Oncology Group (n = 1872), Southwest Oncology Group (n = 359), Eastern Cooperative Oncology Group (n = 397) trials, and in Beat AML (n = 333) and The Cancer Genome Atlas (n = 180) genomic characterization cohorts. We retrospectively analyzed patients in 4 age groups (age range, n): pediatric (0-17, 1744), adolescent\/young adult (18-39, 444), intermediate-age (40-59, 640), older (\u226560, 309).\u00a0IDH\u00a0mutations (IDHmut) were identified in 9.2% of the total cohort (n = 288;\u00a0IDH1\u00a0[n = 123, 42.7%];\u00a0IDH2\u00a0[n = 165, 57.3%]) and were strongly correlated with increased age: 3.4% pediatric vs 21% older,\u00a0P\u00a0&amp;lt; .001. Outcomes were similar in\u00a0IDHmut\u00a0and\u00a0IDH-wildtype (IDHWT) AML (event-free survival [EFS]: 35.6% vs 40.0%,\u00a0P\u00a0= .368; overall survival [OS]: 50.3% vs 55.4%,\u00a0P\u00a0= .196).\u00a0IDH\u00a0mutations frequently occurred with\u00a0NPM1\u00a0(47.2%), DNMT3A\u00a0(29.3%), and\u00a0FLT3-internal tandem duplication (ITD) (22.4%) mutations.\u00a0Patients with\u00a0IDHmut\u00a0AML with\u00a0NPM1\u00a0mutation (IDHmut\/NPM1mut) had significantly improved survival compared with the poor outcomes experienced by patients without (IDHmut\/NPM1WT) (EFS: 55.1% vs 17.0%,\u00a0P\u00a0&amp;lt; .001; OS: 66.5% vs 35.2%,\u00a0P\u00a0&amp;lt; .001).\u00a0DNTM3A\u00a0or\u00a0FLT3-ITD mutations in otherwise favorable\u00a0IDHmut\/NPM1mut\u00a0AML led to inferior outcomes. Age group analysis demonstrated that\u00a0IDH\u00a0mutations did not abrogate the favorable prognostic impact of\u00a0NPM1mut\u00a0in patients aged &amp;lt;60 years; older patients had poor outcomes regardless of\u00a0NPM1\u00a0status.\u00a0These trials were registered at www.clinicaltrials.gov as #NCT00070174, #NCT00372593, #NCT01371981, #NCT00049517, and #NCT00085709.<\/jats:p>","DOI":"10.1182\/bloodadvances.2022008282","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T18:15:21Z","timestamp":1685729721000},"page":"5941-5953","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":68,"title":["Characteristics and prognostic impact of<i>IDH<\/i>mutations in AML: a\u00a0COG, SWOG, and ECOG analysis"],"prefix":"10.1182","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5413-371X","authenticated-orcid":false,"given":"Sara","family":"Zarnegar-Lumley","sequence":"first","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A.","family":"Alonzo","sequence":"additional","affiliation":[{"name":"2Children\u2019s Oncology Group, Monrovia, CA"},{"name":"3University of Southern California Keck School of Medicine, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Gerbing","sequence":"additional","affiliation":[{"name":"2Children\u2019s Oncology Group, Monrovia, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Othus","sequence":"additional","affiliation":[{"name":"4Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoxin","family":"Sun","sequence":"additional","affiliation":[{"name":"5Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda E.","family":"Ries","sequence":"additional","affiliation":[{"name":"6Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Wang","sequence":"additional","affiliation":[{"name":"2Children\u2019s Oncology Group, Monrovia, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Leonti","sequence":"additional","affiliation":[{"name":"6Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew 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