Multi-dimensional analysis of adult acute myeloid leukemia cross-continents reveals age-associated trends in mutational landscape and treatment outcomes (Acute Myeloid Leukemia Cooperative Group & Alliance for Clinical Trials in Oncology)
The outcome of patients with acute myeloid leukemia (AML) worsens with increasing age. Dichotomization into "younger" and "older" patients is clinically routine and often dictates treatment options. We aimed to delineate whether molecular genetic features and/or outcome measures support assorting patient populations by age, including division into "younger" and "older" groups. We analyzed 2823 adult AML patients enrolled onto frontline chemotherapy-based clinical protocols of two cooperative study groups from USA and Germany who were profiled molecularly via targeted sequencing platforms. Frequencies of gene mutations and cytogenetic findings were depicted in 5-year age increments. Clinical outcomes of 2756 AML patients were analyzed with respect to molecular features, genetic-risk groups and age. Age-associated distributions of gene mutations and cytogenetic abnormalities were similar in both cohorts. There was almost linear shortening of overall survival with increasing age among all patients (P < 0.001) and within 2022 European LeukemiaNet-defined genetic-risk groups, with survival decreasing as age increased (favorable-risk, P < 0.001; intermediate-risk, P < 0.001; adverse-risk, P < 0.001). Although mutational profiles and outcomes of the youngest patients differed from those of older patients, there was no age cut-off identifying "younger" and "older" patients. These findings support more age-associated flexibility for drug approval and trial eligibility.
Authors
- John C. Byrd (ORCID: https://orcid.org/0000-0001-9830-0711)
- William Blum (ORCID: https://orcid.org/0000-0003-0111-7465)
- Cristina Sauerland (ORCID: https://orcid.org/0000-0002-8748-8218)
- Maja Rothenberg‐Thurley
- Karsten Spiekermann (ORCID: https://orcid.org/0000-0002-5139-4957)
- Christopher J. Walker (ORCID: https://orcid.org/0000-0002-1819-7388)
- Aarif M.N. Batcha (ORCID: https://orcid.org/0000-0002-7972-7506)
- Utz Krug (ORCID: https://orcid.org/0009-0003-5777-1420)
- Alice S. Mims (ORCID: https://orcid.org/0000-0002-8971-2199)
- Wolfgang E. Berdel (ORCID: https://orcid.org/0000-0002-3030-6567)
- Klaus Hans Metzeler (ORCID: https://orcid.org/0000-0003-3920-7490)
- Philipp A. Greif (ORCID: https://orcid.org/0000-0002-3744-7936)
- Shelley Orwick (ORCID: https://orcid.org/0000-0002-4537-1409)
- Dennis Görlich (ORCID: https://orcid.org/0000-0002-2574-9419)
- Christopher C. Oakes (ORCID: https://orcid.org/0000-0001-8000-9694)
- Monica Cusan (ORCID: https://orcid.org/0000-0003-4907-349X)
- Robert J. Mayer (ORCID: https://orcid.org/0000-0002-9864-7042)
- Bernhard J. Woermann (ORCID: https://orcid.org/0000-0003-2273-5502)
- Vindi Jurinović
- Jonathan E. Kolitz (ORCID: https://orcid.org/0000-0003-2700-4784)
- Richard Maury Stone (ORCID: https://orcid.org/0000-0002-7526-2633)
- Jan Braess (ORCID: https://orcid.org/0000-0001-6528-2078)
- Richard A. Larson (ORCID: https://orcid.org/0000-0001-9168-3203)
- Andrew J. Carroll (ORCID: https://orcid.org/0000-0001-9844-730X)
- Krzysztof Mrózek (ORCID: https://orcid.org/0000-0002-1408-5063)
- James S. Blachly (ORCID: https://orcid.org/0000-0002-4275-5562)
- Tobias Herold (ORCID: https://orcid.org/0000-0002-9615-9432)
- Deedra Nicolet (ORCID: https://orcid.org/0000-0001-7796-0251)
- Ann‐Kathrin Eisfeld (ORCID: https://orcid.org/0000-0001-6442-1419)
- Karilyn Larkin (ORCID: https://orcid.org/0000-0002-1898-9836)
- Stephanie Schneider
- Wolfgang Hiddemann (ORCID: https://orcid.org/0000-0001-7208-4117)
- Joseph O. Moore
- Bayard L. Powell
- Michael C Walker
Institutions
- Atrium Health Wake Forest Baptist (US)
- Northwell Health (US)
- German Society of Surgery (DE)
- Hofstra University (US)
- Emory University (US)
- Duke University (US)
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- University of Münster (DE)
- LMU Klinikum (DE)
- University of Alabama at Birmingham (US)
- University of Illinois Chicago (US)
- University of Chicago (US)
- Munich Leukemia Laboratory (Germany) (DE)
- Zimmer Biomet (Germany) (DE)
- CancerCare (US)
- Dana-Farber Cancer Institute (US)
- Krankenhaus Barmherzige Brüder (DE)
- University Hospital Leipzig (DE)
- Klinikum Leverkusen (DE)
- Wake Forest Baptist Comprehensive Cancer Center
- Deutsches Konsortium für Translationale Krebsforschung (DE)
- The Ohio State University (US)
- University of Cincinnati (US)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Leukemia
- Published
- 2025-09-19
- DOI
- https://doi.org/10.1038/s41375-025-02644-0
- Citations
- 1
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 1.77
Funders
- Ohio State University
- Pelotonia
- José Carreras Leukämie-Stiftung
- National Institutes of Health
- National Cancer Institute