Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a pediatric oncology group study

The relapse rate in childhood acute lymphoblastic leukemia (ALL) is approxi mately 30% but few reinduction regimens have investigated the intensive use of polyethylene glycol Escherichia coli asparaginase (PEG-Asp). Therefore, we assessed the pharmocokinetics and efficacy of PEG-Asp in this setting, Children with B-precursor ALL, in first marrow and/or extramedullary relaps e were eligible. Reinduction included doxorubicin on day 1, prednisone for 28 days, vincristine weekly for 4 weeks, and PEG-Asp either weekly or biwee kly by randomization. Asparaginase levels and antibody to both E coli aspar aginase and PEG-asp were measured weekly just before each PEG-asp dose. Ove rall, 129 of 144 patients (pts) (90%) achieved a complete remission (CR). T here was a highly significant difference in CR rates between weekly (69 of 71; 97%) and biweekly (60 of 73; 82%) PEG-Asp dosing (P = .003). Grade 3 or 4 infectious toxicity was common (50%), but only 4 pts died of sepsis duri ng induction. Other toxicities were infrequent and hypersensitivity was rar e (6 of 144; 4%). Low asparaginase levels were associated with high antibod y titers to either native (P = .024) or PEG asp (P = .0013), The CR rate wa s significantly associated with higher levels of asparaginase (P = .012), P atients with ALL in first relapse receiving weekly PEG-Asp had a higher rat e of second remission compared with biweekly dosing. Low levels of asparagi nase were associated with high antibody titers, Increased asparaginase leve ls may correlate with an improved CR rate. The use of intensive PEG-Asp sho uld be explored further in the treatment of ALL. (C) 2000 by The American S ociety of Hematology.