TY - JOUR
T1 - Prognostic impact of DDX41 germline mutations in intensively treated acute myeloid leukemia patients
T2 - an ALFA-FILO study
AU - Duployez, Nicolas
AU - Largeaud, Laëtitia
AU - Duchmann, Matthieu
AU - Kim, Rathana
AU - Rieunier, Julie
AU - Lambert, Juliette
AU - Bidet, Audrey
AU - Larcher, Lise
AU - Lemoine, Jean
AU - Delhommeau, François
AU - Hirsch, Pierre
AU - Fenwarth, Laurène
AU - Kosmider, Olivier
AU - Decroocq, Justine
AU - Bouvier, Anne
AU - Le Bris, Yannick
AU - Ochmann, Marlène
AU - Santagostino, Alberto
AU - Adès, Lionel
AU - Fenaux, Pierre
AU - Thomas, Xavier
AU - Micol, Jean Baptiste
AU - Gardin, Claude
AU - Itzykson, Raphael
AU - Soulier, Jean
AU - Clappier, Emmanuelle
AU - Recher, Christian
AU - Preudhomme, Claude
AU - Pigneux, Arnaud
AU - Dombret, Hervé
AU - Delabesse, Eric
AU - Sébert, Marie
N1 - Publisher Copyright:
© 2022 American Society of Hematology
PY - 2022/8/18
Y1 - 2022/8/18
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=85130627882&partnerID=8YFLogxK
U2 - 10.1182/blood.2021015328
DO - 10.1182/blood.2021015328
M3 - Article
C2 - 35443031
AN - SCOPUS:85130627882
SN - 0006-4971
VL - 140
SP - 756
EP - 768
JO - Blood
JF - Blood
IS - 7
ER -