title: Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children's Leukemia Group phase 3 trial.
abstract: Asparaginase is an enzyme used in the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma in children. It has minimal bone marrow toxicity. Its major side effects are anaphylaxis, pancreatitis, diabetes, coagulation abnormalities, and thrombosis, especially intracranial. It is derived from 2 different sources: Escherichia coli and Erwinia chrysanthemi. Nonrandomized clinical studies have suggested a similar efficacy of these 2 types of asparaginases and a lower toxicity for Erwinia-asparaginase. The European Organisation for Research and Treatment of Cancer-Children's Leukemia Group (EORTC-CLG) 58881 trial randomized 700 children with acute lymphoblastic leukemia or lymphoblastic lymphoma to either E coli- or Erwinia-asparaginase at the same dosage of 10 000 IU/m(2) twice weekly to compare toxicity and efficacy. Coagulation abnormalities were more frequent in the E coli-asparaginase than in the Erwinia-asparaginase arm of the study (30.2% versus 11.9%, P <.0001). The incidence of other toxicity was not significantly different. In the Erwinia-asparaginase arm, more patients failed to achieve complete remission (4.9% versus 2.0%; P =.038) and the relapse rate was higher, leading to shorter event-free survival (hazard ratio,1.59; 95% CI, 1.23-2.06; P =.0004). The estimate of event-free survival rate (SE) at 6 years was 59.8% (2.6%) versus 73.4% (2.4%). Overall survival rate at 6 years was also lower in the Erwinia-asparaginase arm at 75.1% (2.3%) versus 83.9% (2.0%), P =.002. With the dose scheduling used in this protocol, E coli-asparaginase induced more coagulation abnormalities but was superior to Erwinia-asparaginase for the treatment of childhood lymphoid malignancies.
authors.affiliation: Service d'Hémato-Immunologie, Hôpital Robert-Debré, Paris, France. michel.duval@umontreal.ca
authors.forename: Michel
authors.initials: M
authors.lastname: Duval
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Alina
authors.initials: A
authors.lastname: Ferster
authors.forename: Xavier
authors.initials: X
authors.lastname: Rialland
authors.forename: Brigitte
authors.initials: B
authors.lastname: Nelken
authors.forename: Patrick
authors.initials: P
authors.lastname: Lutz
authors.forename: Yves
authors.initials: Y
authors.lastname: Benoit
authors.forename: Alain
authors.initials: A
authors.lastname: Robert
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Manel
authors.forename: Etienne
authors.initials: E
authors.lastname: Vilmer
authors.forename: Jacques
authors.initials: J
authors.lastname: Otten
authors.forename: Noël
authors.initials: N
authors.lastname: Philippe
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000592:standards / Q000633:toxicity; D001215:Asparaginase / Q000008:administration & dosage* / Q000592:standards / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D004885:Erwinia / Q000201:enzymology*; D004926:Escherichia coli / Q000201:enzymology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy; D012074:Remission Induction / Q000379:methods; D013810:Therapeutic Equivalency
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase