%0 Journal Article %T Prognostic significance of concurrent gene mutations i n intensively treated patients with IDH-mutated AML: an ALFA study %+ Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)) %+ Hopital Saint-Louis [AP-HP] (AP-HP) %+ Institut Gustave Roussy (IGR) %+ Université Paris-Saclay %+ Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER) %+ CHU Lille %+ Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH) (IRSL) %+ Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS) %+ CHU Amiens-Picardie %+ Hôpital Avicenne [AP-HP] %+ Recherche clinique appliquée à l'hématologie ((EA_3518)) %+ Université Paris Cité (UPCité) %+ CHU Caen %+ Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel) %+ Hôpital d'instruction des Armées Percy %+ Hôpital Henri Mondor %+ Centre Hospitalier de Versailles André Mignot (CHV) %+ CHU Dijon %+ Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges] %+ Institut Paoli-Calmettes (IPC) %+ Hôpital Haut-Lévêque [CHU Bordeaux] %+ Service Hématologie - IUCT-Oncopole [CHU Toulouse] %A Duchmann, Matthieu %A Micol, Jean-Baptiste %A Duployez, Nicolas %A Raffoux, Emmanuel %A Thomas, Xavier %A Marolleau, Jean-Pierre %A Braun, Thorsten %A Ades, Lionel %A Chantepie, Sylvain %A Lemasle, Emilie %A Berthon, Celine %A Malfuson, Jean-Valere %A Pautas, Cecile %A Lambert, Juliette %A Boissel, Nicolas %A Celli-Lebras, Karine %A Caillot, Denis %A Turlure, Pascal %A Vey, Norbert %A Pigneux, Arnaud %A Recher, Christian %A Terre, Christine %A Gardin, Claude %A Itzykson, Raphael %A Preudhomme, Claude %A Dombret, Herve %A Botton, Stephane, De %< avec comité de lecture %@ 0006-4971 %J Blood %I American Society of Hematology %V 137 %N 20 %P 2827-2837 %8 2021 %D 2021 %R 10.1182/blood.2020010165 %M 33881523 %Z Life Sciences [q-bio]Journal articles %X In patients with isocitrate dehydrogenase (IDH)-mutated acute myeloid leukemia (AML) treated by intensive chemotherapy (IC), prognostic significance of co-occurring genetic alterations and allogeneic hematopoietic stem cell transplantation (HSCT) are of particular interest with the advent of IDH1/2 mutant inhibitors. We retrospectively analyzed 319 patients with newly diagnosed AML (127 with IDH1, 135 with IDH2R140, and 57 with IDH2R172 mutations) treated with IC in 3 Acute Leukemia French Association prospective trials. In each IDH subgroup, we analyzed the prognostic impact of clinical and genetic covariates, and the role of HSCT. In patients with IDH1 mutations, the presence of NPM1 mutations was the only variable predicting improved overall survival (OS) in multivariate analysis (P< .0001). In IDH2R140-mutated AML, normal karyotype (P = .008) and NPM1 mutations (P = .01) predicted better OS. NPM1 mutations were associated with better disease-free survival (DFS; P = .0009), whereas the presence of DNMT3A mutations was associated with shorter DFS (P = .0006). In IDH2R172-mutated AML, platelet count was the only variable retained in the multivariate model for OS (P = .002). Among nonfavorable European LeukemiaNet 2010-eligible patients, 71 (36%) underwent HSCT in first complete remission (CR1) and had longer OS (P = .03) and DFS (P = .02) than nontransplanted patients. Future clinical trials testing frontline IDH inhibitors combined with IC may consider stratification on NPM1 mutational status, the primary prognostic factor in IDH1- or IDH2R140-mutated AML. HSCT improve OS of nonfavorable IDH1/2-mutated AML and should be fully integrated into the treatment strategy. %G English %2 https://u-picardie.hal.science/hal-03604929/document %2 https://u-picardie.hal.science/hal-03604929/file/S0006497121004250.pdf %L hal-03604929 %U https://u-picardie.hal.science/hal-03604929 %~ INSERM %~ SSA %~ RIIP %~ HCL %~ CNRS %~ CDF %~ APHP %~ CHLS %~ FNCLCC %~ IGR %~ PAOLI_CALMETTES %~ BECQUEREL %~ COMUE-NORMANDIE %~ PSL %~ UNIV-PARIS-SACLAY %~ UNIV-LILLE %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SANTE %~ CDF-PSL %~ UNIVERSITE-PARIS-SACLAY %~ CANTHER %~ U-PICARDIE %~ HEMATIM %~ ELSEVIER