1. Added prognostic value of secondary AML-like gene mutations in ELN intermediate-risk older AML: ALFA-1200 study results
- Author
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Mauricette Michallet, Emilie Lemasle, Claude Preudhomme, Lauris Gastaud, Nicolas Boissel, Karine Celli-Lebras, Christine Terré, Thorsten Braun, Régis Peffault de Latour, Juliette Lambert, Nicolas Duployez, Elise Fournier, Claude Gardin, Raphael Itzykson, Hervé Dombret, Stéphane de Botton, Lionel Ades, Cécile Pautas, Céline Berthon, Jean-Henri Bourhis, Emmanuel Raffoux, Jean-Pierre Marolleau, Jean-Valère Malfuson, Sylvain Chantepie, Thomas Cluzeau, Xavier Thomas, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Henri Mondor, Hôpital Claude Huriez [Lille], CHU Lille, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], CHU Amiens-Picardie, Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Léon Bérard [Lyon], Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Hopital Saint-Louis [AP-HP] (AP-HP)
- Subjects
Oncology ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Gene mutation ,03 medical and health sciences ,European LeukemiaNet ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,030304 developmental biology ,Aged ,0303 health sciences ,Acute leukemia ,Myeloid Neoplasia ,business.industry ,Myelodysplastic syndromes ,Hazard ratio ,Neoplasms, Second Primary ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Chemotherapy regimen ,3. Good health ,Transplantation ,Leukemia ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,Myelodysplastic Syndromes ,Mutation ,business - 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.
- Published
- 2019