Fiche publication
Date publication
juillet 2017
Journal
Haematologica
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MUNZER Martine
Tous les auteurs :
Mondelaers V, Suciu S, De Moerloose B, Ferster A, Mazingue F, Plat G, Yakouben K, Uyttebroeck A, Lutz P, Costa V, Sirvent N, Plouvier E, Munzer M, Poirée M, Minckes O, Millot F, Plantaz D, Maes P, Hoyoux C, Cave' H, Rohrlich P, Bertrand Y, Benoit Y
Lien Pubmed
Résumé
Asparaginase is an essential component of combination chemotherapy for childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma. The value of asparaginase was further addressed in a group of non-very high risk patients by comparing a prolonged (long-asparaginase) versus standard (short-asparaginase) native E.coli asparaginase treatment through a randomized question as part of the phase III 58951 trial of the European Organisation for Research and Treatment of Cancer Children's Leukemia Group. The main endpoint was disease-free survival. Overall, 1,552 patients were randomly assigned to long-asparaginase (775 patients) or short-asparaginase (777 patients). Patients with grade≥2 allergy to native E.coli asparaginase were switched to equivalent doses of Erwinia or pegylated E.coli asparaginase. The 8-year disease-free survival rate (±standard error) was 87.0+/-1.3% in the long-asparaginase and 84.4±1.4% in the short-asparaginase group (hazard ratio:0.87, P=0.33) and the 8-year overall survival rate was 92.6&+/-1.0% and 91.3+/-1.2% respectively (hazard ratio:0.89, P=0.53). An exploratory analysis suggested that the impact of long-asparaginase was beneficial in National Cancer Institute standard risk group regarding disease-free survival (hazard ratio: 0.70; P=0.057), but was far less regarding overall survival (hazard ratio: 0.89). The incidence of grade 3-4 infection during consolidation (25.2% versus 14.4%) and late intensification (22.6% versus 15.9%) and the incidence of grade 2-4 allergy were higher in the long-asparaginase arm (30% versus 21%). Prolonged native E.coli asparaginase therapy in consolidation and late intensification for our non-very high risk patients did not improve overall outcome but led to an increase in infections and allergy. This trial was registered at www.clinicaltrials.gov as #NCT00003728.
Mots clés
Adolescent, Antineoplastic Agents, administration & dosage, Asparaginase, administration & dosage, Child, Child, Preschool, Consolidation Chemotherapy, Escherichia coli Proteins, administration & dosage, Female, Humans, Induction Chemotherapy, Infant, Lymphoma, Non-Hodgkin, diagnosis, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma, diagnosis, Survival Analysis, Time Factors, Treatment Outcome
Référence
Haematologica. 2017 Jul;:
