Added prognostic value of secondary AML-like gene mutations in ELN intermediate-risk older AML: ALFA-1200 study results

Author:

Gardin Claude1,Pautas Cécile2,Fournier Elise3,Itzykson Raphaël4ORCID,Lemasle Emilie5,Bourhis Jean-Henri6,Adès Lionel4ORCID,Marolleau Jean-Pierre7,Malfuson Jean-Valère8,Gastaud Lauris9,Raffoux Emmanuel4,Lambert Juliette10,Braun Thorsten1,Thomas Xavier11ORCID,Chantepie Sylvain12ORCID,Cluzeau Thomas13,de Botton Stéphane6,Berthon Céline14,Boissel Nicolas4,Duployez Nicolas3ORCID,Terré Christine15,Peffault de Latour Régis4,Michallet Mauricette11,Celli-Lebras Karine16,Preudhomme Claude3ORCID,Dombret Hervé4ORCID

Affiliation:

1. Department of Hematology, Université Paris Nord, Hôpital Avicenne, Assistance Publique–Hôpitaux de Paris, Bobigny, France;

2. Department of Hematology, Hôpital Henri Mondor, Assistance Publique–Hôpitaux de Paris, Créteil, France;

3. Department of Hematology, INSERM UMR-S 1172, Biology and Pathology Center, Université de Lille, Centre Hospitalier Universitaire Claude Huriez, Lille, France;

4. Department of Hematology, Saint-Louis Institute for Research, Université de Paris, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris, Paris, France;

5. Department of Hematology, Henri-Becquerel Center, Rouen, France;

6. Department of Hematology, Institut Gustave Roussy, Villejuif, France;

7. Department of Hematology, Centre Hospitalier Universitaire, Amiens, France;

8. Department of Hematology, Hôpital Percy, Clamart, France;

9. Department of Hematology, Centre Antoine Lacassagne, Nice, France;

10. Department of Hematology, Hôpital André Mignot, Université de Versailles-Saint Quentin, Versailles, France;

11. Service d’Hématologie, Centre Léon Bérard, Lyon, France;

12. Department of Hematology, Centre Hospitalier Universitaire, Caen, France;

13. Department of Hematology, Centre Hospitalier Universitaire, Nice, France;

14. Department of Hematology, Centre Hospitalier Universitaire Claude Huriez, Lille, France;

15. Laboratory of Cytogenetics, Hôpital André Mignot, Université de Versailles-Saint Quentin, Versailles, France; and

16. Acute Leukemia French Association, Office for Clinical Research in Hematology and Immunodeficiency, Saint-Louis Institute, Université de Paris, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris, Paris, France

Abstract

Abstract In this study, we aimed to refine prognostication of older with acute myeloid leukemia (AML) after intensive chemotherapy. Five hundred and nine patients aged 60 years or older (median age, 68 years) were prospectively enrolled in the intensive Acute Leukemia French Association (ALFA)-1200 trial between 2012 and 2016, and 471 patient samples were submitted to multigene analysis. Mutations in any of 8 genes frequently altered in myelodysplastic syndromes (MDS), including ASXL1, SRSF2, STAG2, BCOR, U2AF1, EZH2, SF3B1, and ZRSR2, defined a secondary AML (sAML)-like disease, as reported. Of the samples analyzed, 48% included sAML-like gene mutations. These mutations were associated with a shorter event-free survival, both overall (hazard ratio, 1.46; 95% confidence interval, 1.19-1.79; P < .001) and within the European LeukemiaNet (ELN)-2017 intermediate-risk subgroup (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28; P = .044), which excludes ASXL1-mutated cases by definition. We therefore included patients with intermediate-risk AML carrying sAML-like mutations in a single high-risk patients group together with adverse-risk patients with AML, whereas other intermediate-risk patients were included in a standard-risk group together with favorable-risk patients (high-risk/standard-risk patient ratio, 1.00). Using this 2-class risk assessment, we observed that transplantation prolonged overall survival from remission in patients with high-risk AML only, not in patients with standard-risk AML. Routine analysis of sAML-like gene mutations may thus improve the definition of high-risk older patients with AML, and better identify the half of older patients who clearly derive survival benefit from allogeneic transplantation in first remission. This trial was registered at www.clinicaltrials.gov as #NCT01966497.

Publisher

American Society of Hematology

Subject

Hematology

Cited by 58 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3