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Prognostic impact of DDX41 germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study.
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; Sébert, Marie.
Afiliação
  • Duployez N; Hematology Laboratory, Unité 1277-Cancer Heterogeneity Plasticity and Resistance to Therapies (CANTHER), Centre Hospitalier Universitaire (CHU) de Lille, University of Lille, INSERM, Lille, France.
  • Largeaud L; Hematology Laboratory, CHU de Toulouse-Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
  • Duchmann M; Université de Paris, Unité 944/7212-GenCellDi, INSERM and Centre National de la Recherche Scientifique (CNRS), Paris, France.
  • Kim R; Université de Paris, Unité 944/7212-GenCellDi, INSERM and Centre National de la Recherche Scientifique (CNRS), Paris, France.
  • Rieunier J; Hematology Laboratory, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Lambert J; Hematology Laboratory, CHU de Toulouse-Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
  • Bidet A; Hematology Department, Versailles Hospital, Le Chesnay, France.
  • Larcher L; Hematology Laboratory, CHU de Bordeaux, Bordeaux, France.
  • Lemoine J; Université de Paris, Unité 944/7212-GenCellDi, INSERM and Centre National de la Recherche Scientifique (CNRS), Paris, France.
  • Delhommeau F; Hematology Laboratory, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Hirsch P; Hematology Department, Saint Louis Hospital, AP-HP, Paris, France.
  • Fenwarth L; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Laboratoire d'hématologie biologique, Hôpital Saint-Antoine, Paris, France.
  • Kosmider O; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Laboratoire d'hématologie biologique, Hôpital Saint-Antoine, Paris, France.
  • Decroocq J; Hematology Laboratory, Unité 1277-Cancer Heterogeneity Plasticity and Resistance to Therapies (CANTHER), Centre Hospitalier Universitaire (CHU) de Lille, University of Lille, INSERM, Lille, France.
  • Bouvier A; Hematology Laboratory, Cochin Hospital, AP-HP, Paris, France.
  • Le Bris Y; Hematology Department, Cochin Hospital, AP-HP, Paris, France.
  • Ochmann M; Hematology Laboratory, CHU Angers, Angers, France.
  • Santagostino A; Hematology Biology, Nantes University Hospital, Nantes, France.
  • Adès L; CRCINA, INSERM, CNRS, Université de Nantes, Université d'Angers, Nantes, France.
  • Fenaux P; Hematology Department, CHU Orléans, Orléans, France.
  • Thomas X; Hematology Department, CHU Troyes, Troyes, France.
  • Micol JB; Université de Paris, Unité 944/7212-GenCellDi, INSERM and Centre National de la Recherche Scientifique (CNRS), Paris, France.
  • Gardin C; Hematology Department, Saint Louis Hospital, AP-HP, Paris, France.
  • Itzykson R; Université de Paris, Unité 944/7212-GenCellDi, INSERM and Centre National de la Recherche Scientifique (CNRS), Paris, France.
  • Soulier J; Hematology Department, Saint Louis Hospital, AP-HP, Paris, France.
  • Clappier E; Hematology Department, Hospices Civils de Lyon, Lyon-Sud Hospital, Lyon, France.
  • Recher C; Hematology Department, Gustave Roussy Institute, University of Paris-Saclay, Villejuif, France.
  • Preudhomme C; Hematology Department, Avicenne Hospital, AP-HP, Bobigny, France.
  • Pigneux A; Unité 3518, Saint-Louis Institute for Research, Université de Paris, Paris, France.
  • Dombret H; Université de Paris, Unité 944/7212-GenCellDi, INSERM and Centre National de la Recherche Scientifique (CNRS), Paris, France.
  • Delabesse E; Hematology Department, Saint Louis Hospital, AP-HP, Paris, France.
  • Sébert M; Université de Paris, Unité 944/7212-GenCellDi, INSERM and Centre National de la Recherche Scientifique (CNRS), Paris, France.
Blood ; 140(7): 756-768, 2022 08 18.
Article em En | MEDLINE | ID: mdl-35443031
ABSTRACT
DDX41 germline mutations (DDX41MutGL) are the most common genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia (AML). Recent reports suggest that DDX41MutGL myeloid malignancies could be considered as a distinct entity, even if their specific presentation and outcome remain to be defined. We describe here the clinical and biological features of 191 patients with DDX41MutGL AML. Baseline characteristics and outcome of 86 of these patients, treated with intensive chemotherapy in 5 prospective Acute Leukemia French Association/French Innovative Leukemia Organization trials, were compared with those of 1604 patients with DDX41 wild-type (DDX41WT) AML, representing a prevalence of 5%. Patients with DDX41MutGL AML were mostly male (75%), in their seventh decade, and with low leukocyte count (median, 2 × 109/L), low bone marrow blast infiltration (median, 33%), normal cytogenetics (75%), and few additional somatic mutations (median, 2). A second somatic DDX41 mutation (DDX41MutSom) was found in 82% of patients, and clonal architecture inference suggested that it could be the main driver for AML progression. DDX41MutGL patients displayed higher complete remission rates (94% vs 69%; P < .0001) and longer restricted mean overall survival censored at hematopoietic stem cell transplantation (HSCT) than 2017 European LeukemiaNet intermediate/adverse (Int/Adv) DDX41WT patients (5-year difference in restricted mean survival times, 13.6 months; P < .001). Relapse rates censored at HSCT were lower at 1 year in DDX41MutGL patients (15% vs 44%) but later increased to be similar to Int/Adv DDX41WT patients at 3 years (82% vs 75%). HSCT in first complete remission was associated with prolonged relapse-free survival (hazard ratio, 0.43; 95% confidence interval, 0.21-0.88; P = .02) but not with longer overall survival (hazard ratio, 0.77; 95% confidence interval, 0.35-1.68; P = .5).
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Transplante de Células-Tronco Hematopoéticas Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Blood Ano de publicação: 2022 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Transplante de Células-Tronco Hematopoéticas Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Blood Ano de publicação: 2022 Tipo de documento: Article País de afiliação: França