Characteristics and prognostic impact of IDH mutations in AML: a COG, SWOG, and ECOG analysis

Sara Zarnegar-Lumley, Todd A. Alonzo, Robert B. Gerbing, Megan Othus, Zhuoxin Sun, Rhonda E. Ries, Jim Wang, Amanda Leonti, Matthew A. Kutny, Fabiana Ostronoff, Jerald P. Radich, Frederick R. Appelbaum, Era L. Pogosova-Agadjanyan, Kristen O’Dwyer, Martin S. Tallman, Mark Litzow, Ehab Atallah, Todd M. Cooper, Richard A. Aplenc, Omar Abdel-WahabAlan S. Gamis, Selina Luger, Harry Erba, Ross Levine, E. Anders Kolb, Derek L. Stirewalt, Soheil Meshinchi, Katherine Tarlock

Research output: Contribution to journalArticlepeer-review

Abstract

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 IDH mutations in AML across age. Our cohort included 3141 patients aged between <1 month and 88 years treated on Children’s Cancer Group/Children’s 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 (≥60, 309). IDH mutations (IDHmut) were identified in 9.2% of the total cohort (n = 288; IDH1 [n = 123, 42.7%]; IDH2 [n = 165, 57.3%]) and were strongly correlated with increased age: 3.4% pediatric vs 21% older, P < .001. Outcomes were similar in IDHmut and IDH-wildtype (IDHWT) AML (event-free survival [EFS]: 35.6% vs 40.0%, P = .368; overall survival [OS]: 50.3% vs 55.4%, P = .196). IDH mutations frequently occurred with NPM1 (47.2%), DNMT3A (29.3%), and FLT3-internal tandem duplication (ITD) (22.4%)

Original languageEnglish (US)
Pages (from-to)5941-5953
Number of pages13
JournalBlood Advances
Volume7
Issue number19
DOIs
StatePublished - Oct 10 2023

ASJC Scopus subject areas

  • Hematology

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