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).

IF 13.4 1区 医学 Q1 HEMATOLOGY
Monica Cusan,Karilyn Larkin,Deedra Nicolet,Vindi Jurinovic,Krzysztof Mrózek,Aarif M N Batcha,Maja Rothenberg-Thurley,Stephanie Schneider,Cristina Sauerland,Dennis Görlich,Utz Krug,Wolfgang E Berdel,Bernhard J Woermann,Wolfgang Hiddemann,Jan Braess,Karsten Spiekermann,Philipp A Greif,James S Blachly,Alice S Mims,Christopher J Walker,Michael C Walker,Christopher C Oakes,Shelley Orwick,Andrew J Carroll,William G Blum,Bayard L Powell,Jonathan E Kolitz,Joseph O Moore,Robert J Mayer,Richard A Larson,Richard M Stone,John C Byrd,Klaus H Metzeler,Tobias Herold,Ann-Kathrin Eisfeld
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Abstract

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.
跨大洲成人急性髓性白血病的多维分析揭示了突变景观和治疗结果的年龄相关趋势(急性髓性白血病肿瘤临床试验合作小组和联盟)。
急性髓性白血病(AML)患者的预后随着年龄的增长而恶化。将患者分为“年轻”和“年长”是临床上的常规做法,并经常决定治疗方案。我们的目的是描述分子遗传特征和/或结果测量是否支持按年龄分类患者群体,包括分为“年轻”和“老年”群体。我们分析了2823名成年AML患者,这些患者加入了来自美国和德国的两个合作研究组的一线化疗临床方案,这些患者通过靶向测序平台进行了分子谱分析。基因突变频率和细胞遗传学结果以5岁为单位进行描述。分析2756例AML患者的分子特征、遗传风险组和年龄的临床结局。在两个队列中,年龄相关的基因突变和细胞遗传学异常分布相似。在所有患者中,随着年龄的增加,总生存率几乎呈线性缩短(P < 0.001),在2022年欧洲白血病网定义的遗传风险组中,生存率随着年龄的增加而下降(有利风险,P < 0.001;中等风险,P < 0.001;不利风险,P < 0.001)。尽管年轻患者的突变特征和结果与老年患者不同,但没有年龄界限来确定“年轻”和“老年”患者。这些发现支持在药物审批和试验资格方面有更多与年龄相关的灵活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
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