Cusan Monica, Larkin Karilyn, Nicolet Deedra, Jurinovic Vindi, Mrózek Krzysztof, Batcha Aarif M N, Rothenberg-Thurley Maja, Schneider Stephanie, Sauerland Cristina, Görlich Dennis, Krug Utz, Berdel Wolfgang E, Woermann Bernhard J, Hiddemann Wolfgang, Braess Jan, Spiekermann Karsten, Greif Philipp A, Blachly James S, Mims Alice S, Walker Christopher J, Walker Michael C, Oakes Christopher C, Orwick Shelley, Carroll Andrew J, Blum William G, Powell Bayard L, Kolitz Jonathan E, Moore Joseph O, Mayer Robert J, Larson Richard A, Stone Richard M, Byrd John C, Metzeler Klaus H, Herold Tobias, Eisfeld Ann-Kathrin
Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Leukemia. 2025 Sep 19. doi: 10.1038/s41375-025-02644-0.
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.
急性髓系白血病（AML）患者的预后随年龄增长而恶化。临床上通常将患者分为“年轻”和“老年”两组，并常常据此决定治疗方案。我们旨在确定分子遗传学特征和/或预后指标是否支持按年龄对患者群体进行分类，包括分为“年轻”和“老年”组。我们分析了2823例成年AML患者，这些患者参加了美国和德国两个合作研究组基于一线化疗的临床方案，并通过靶向测序平台进行了分子特征分析。基因突变频率和细胞遗传学结果按5岁年龄增量进行描述。对2756例AML患者的临床预后进行了分子特征、遗传风险组和年龄方面的分析。两个队列中基因突变和细胞遗传学异常的年龄相关分布相似。在所有患者中（P < 0.001）以及在2022年欧洲白血病网定义的遗传风险组内，总体生存期几乎随年龄增长呈线性缩短，生存率随年龄增加而降低（低危，P < 0.001；中危，P < 0.001；高危，P < 0.001）。尽管最年轻患者的突变谱和预后与老年患者不同，但没有年龄界限可区分“年轻”和“老年”患者。这些发现支持在药物批准和试验资格方面更具年龄相关性的灵活性。
