Document Type
Article
Publication Date
10-10-2023
Identifier
DOI: 10.1182/bloodadvances.2022008282; PMCID: PMC10562769
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 betweenChildren'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%) mutations. Patients with IDHmut AML with NPM1 mutation (IDHmut/NPM1mut) had significantly improved survival compared with the poor outcomes experienced by patients without (IDHmut/NPM1WT) (EFS: 55.1% vs 17.0%, P < .001; OS: 66.5% vs 35.2%, P < .001). DNTM3A or FLT3-ITD mutations in otherwise favorable IDHmut/NPM1mut AML led to inferior outcomes. Age group analysis demonstrated that IDH mutations did not abrogate the favorable prognostic impact of NPM1mut in patients aged < 60 years; older patients had poor outcomes regardless of NPM1 status. These trials were registered at www.clinicaltrials.gov as #NCT00070174, #NCT00372593, #NCT01371981, #NCT00049517, and #NCT00085709.
Journal Title
Blood Adv
Volume
7
Issue
19
First Page
5941
Last Page
5953
MeSH Keywords
Adolescent; Young Adult; Humans; Child; Infant; Child, Preschool; Prognosis; Isocitrate Dehydrogenase; Nucleophosmin; Retrospective Studies; Leukemia, Myeloid, Acute; Mutation
Keywords
Prognosis; Isocitrate Dehydrogenase; Nucleophosmin; Retrospective Studies; Acute Myeloid Leukemia; Mutation
Recommended Citation
Zarnegar-Lumley S, Alonzo TA, Gerbing RB, et al. Characteristics and prognostic impact of IDH mutations in AML: a COG, SWOG, and ECOG analysis. Blood Adv. 2023;7(19):5941-5953. doi:10.1182/bloodadvances.2022008282
Comments
This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.
Publisher's Link:
https://ashpublications.org/bloodadvances/article/7/19/5941/496147/Characteristics-and-prognostic-impact-of-IDH