Efficacy and safety of recombinant E. coli E. coli asparaginase in children with previously untreated acute lymphoblastic leukemia: A randomized multicenter study of the Dutch Childhood Oncology Group

摘要

Abstract Background The efficacy and safety of recombinant Escherichia coli –asparaginase (rASNase) was compared to native E.coli asparaginase (Asparaginase medac). Methods One hundred and ninety‐nine children with newly diagnosed acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5,000 U/m2 during induction (eight doses) and 10,000 U/m2 during the postinduction phase (only high‐risk patients; standard‐ and medium‐risk patients received pegaspargase). Results Median trough serum asparaginase activity levels were comparable between both groups; they ranged from 143 to 182?U/l during induction and were above the target value of 100?U/l. Complete asparagine depletion in serum was achieved in 97.9% of patients, with no significant differences between both groups. On day 33 (end of induction), only two (2%) evaluable patients in each group had measurable asparagine serum levels, and complete asparagine depletion in the cerebrospinal fluid was achieved in 98.8% and 93.6% of the patients with rASNase and Asparaginase medac, respectively. During induction, 2.1% and 5% of patients developed an allergic reaction to rASNase or Asparaginase medac, respectively. Approximately 41% of the patients in both groups had a clinical allergy or enzyme inactivation to the first dose of any asparaginase preparation in postinduction. A comparable proportion of patients in both groups developed anti‐asparaginase antibodies (57%) during repeated administration of asparaginase. Minimal residual disease levels at the end of induction, 5‐year event‐free survival, and 5‐year cumulative incidence of relapse did not differ between both groups. Conclusion The efficacy, safety, and immunogenicity of both asparaginase preparations are comparable. This trial was registered at www.clinicaltrials.gov as #NCT00784017; EudraCT number 2006‐003180‐31.