1. Prognostic impact of DDX41germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study
- Author
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Duployez, Nicolas, Largeaud, Laëtitia, Duchmann, Matthieu, Kim, Rathana, Rieunier, Julie, Lambert, Juliette, Bidet, Audrey, Larcher, Lise, Lemoine, Jean, Delhommeau, François, Hirsch, Pierre, Fenwarth, Laurène, Kosmider, Olivier, Decroocq, Justine, Bouvier, Anne, Le Bris, Yannick, Ochmann, Marlène, Santagostino, Alberto, Adès, Lionel, Fenaux, Pierre, Thomas, Xavier, Micol, Jean-Baptiste, Gardin, Claude, Itzykson, Raphael, Soulier, Jean, Clappier, Emmanuelle, Recher, Christian, Preudhomme, Claude, Pigneux, Arnaud, Dombret, Hervé, Delabesse, Eric, and Sébert, Marie
- Abstract
DDX41germline mutations (DDX41MutGL) are the most common genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia (AML). Recent reports suggest that DDX41MutGLmyeloid malignancies could be considered as a distinct entity, even if their specific presentation and outcome remain to be defined. We described here the clinical and biological features of 191 patients with DDX41MutGLAML. Baseline characteristics and outcome of 86 of them, treated with intensive chemotherapy in 5 prospective ALFA/FILO trials were compared with those of 1604 DDX41wild-type (DDX41WT) AML patients, representing a prevalence of 5%. DDX41MutGLAML patients were mostly males (75%) in their seventh decade, with low leukocyte count (median, 2x109/L), low bone marrow blast infiltration (median, 33%), normal cytogenetics (75%) and few additional somatic mutations (median, 2). A second somatic DDX41mutation (DDX41MutSom) was found in 82% of patients and clonal architecture inference suggested that it could be the main driver for AML progression. DDX41MutGLpatients displayed higher complete remission (CR) rates (94% vs.69%, p<0.0001) and longer restricted mean overall survival (OS) censored at hematopoietic stem cell transplantation (HSCT) than ELN-2017 intermediate/adverse (Int/Adv) DDX41WTpatients (5-year ΔRMST of 13.6 months, p < 0.001). Relapse rates censored at HSCT were lower at 1 year in DDX41MutGLpatients (15% vs.44%) but later increased to join that of Int/Adv DDX41WTpatients at 3 years (82% vs 75%). HSCT in first CR was associated with prolonged relapse-free survival (RFS; HR, 0.43 [95%CI, 0.21-0.88]; p = 0.02) but not with longer OS (HR=0.77 [95%CI, 0.35-1.68], p=0.5).
- Published
- 2024
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