Title :

Genetic identification of patients with AML older than 60 years achieving long-term survival with intensive chemotherapy

Author(s) :

Itzykson, Raphael [Auteur]
Génomes, biologie cellulaire et thérapeutiques [GenCellDi (U944 / UMR7212)]
Fournier, Elise [Auteur]
Hôpital Claude Huriez [Lille]
Berthon, Celine [Auteur]
Rollig, Christoph [Auteur]
Technische Universität Dresden = Dresden University of Technology [TU Dresden]
Braun, Thorsten [Auteur]
Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
Marceau-Renaut, Alice [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Pautas, Cecile [Auteur]
Service d'hématologie clinique
Nibourel, Olivier [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Service d'Hématologie Cellulaire [Lille]
Lemasle, Emilie [Auteur]
Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen [CLCC Henri Becquerel]
Micol, Jean-Baptiste [Auteur]
Cellules souches hématopoïétiques et développement des hémopathies myéloïdes [CSHMyelo]
Ades, Lionel [Auteur]
Université Paris Cité [UPCité]
Hopital Saint-Louis [AP-HP] [AP-HP]
Lebon, Delphine [Auteur]
HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 [HEMATIM]
CHU Amiens-Picardie
Malfuson, Jean-Valere [Auteur]
Centre de Transfusion Sanguine des Armées [CTSA]
Gastaud, Lauris [Auteur]
Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] [UNICANCER/CAL]
Goursaud, laure [Auteur]
Etablissement français du sang [Rennes] [EFS Bretagne]
Raffoux, Emmanuel [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Wattebled, Kevin-James [Auteur]
Rousselot, Philippe [Auteur]
Centre Hospitalier de Versailles André Mignot [CHV]
Thomas, Xavier [Auteur]
Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS]
Chantepie, Sylvain [Auteur]
Institut d'Hématologie de Basse-Normandie [IHBN]
Cluzeau, Thomas [Auteur]
XLIM [XLIM]
Serve, Hubert [Auteur]
Boissel, Nicolas [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Terre, Christine [Auteur]
Centre Hospitalier de Versailles André Mignot [CHV]
Celli-Lebras, Karine [Auteur]
Preudhomme, Claude [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Thiede, Christian [Auteur]
Technische Universität Dresden = Dresden University of Technology [TU Dresden]
Dombret, Herve [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Gardin, Claude [Auteur]
Hôpital Avicenne [AP-HP]
Duployez, Nicolas [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]

Journal title :

Blood

Pages :

507-519

Publisher :

American Society of Hematology

Publication date :

2021

ISSN :

0006-4971

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

To design a simple and reproducible classifier predicting the overall survival (OS) of patients with acute myeloid leukemia (AML) >= 60 years of age treated with 7+3, we sequenced 37 genes in 471patients fromtheALFA1200 ...
Show more >To design a simple and reproducible classifier predicting the overall survival (OS) of patients with acute myeloid leukemia (AML) >= 60 years of age treated with 7+3, we sequenced 37 genes in 471patients fromtheALFA1200 (Acute Leukemia FrenchAssociation) study (median age, 68 years). Mutation patterns and OS differed between the 84 patients with poor-risk cytogenetics and the 387 patientswith good (n = 13), intermediate (n = 339), or unmeasured (n = 35) cytogenetic risk. TP53 (hazards ratio [HR], 2.49; P = .0003) and KRAS (HR, 3.60; P = .001) mutations independently worsened the OS of patients with poor-risk cytogenetics. In those without poor-risk cytogenetics, NPM1 (HR, 0.57; P = .0004), FLT3 internal tandem duplications with low (HR, 1.85; P = .0005) or high (HR, 3.51; P < 10(-4)) allelic ratio, DNMT3A (HR, 1.86; P < 10(-4)), NRAS (HR, 1.54; P = .019), and ASXL1 (HR, 1.89; P=.0003) mutations independently predicted OS. Combining cytogenetic risk and mutations in these 7 genes, 39.1% of patients could be assigned to a ``go-go'' tier with a 2-year OS of 66.1%, 7.6% to the ``no-go'' group (2-year OS 2.8%), and 3.3% of to the ``slow-go'' group (2-year OS of 39.1%; P < 10(-5)). Across 3 independent validation cohorts, 31.2% to 37.7% and 11.2% to 13.5% of patients were assigned to the go-go and the no-go tiers, respectively, with significant differences inOS between tiers in all 3 trial cohorts (HDF [Hauts-de-France], n = 141, P = .003; andSAL [StudyAlliance Leukemia], n=46; AMLSG [AML Study Group], n = 223, both P < 10(-5)). The ALFA decision tool is a simple, robust, and discriminant prognostic model for AML patients >= 60 years of age treated with intensive chemotherapy. This model can instruct the design of trials comparing the 7+3 standard of care with less intensive regimens.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL