Polyethylene Glycol-Conjugated L-Asparaginase Versus Native L-Asparaginase In Combination With Standard Agents For Children With Acute Lymphoblastic Leukemia In Second Bone Marrow Relapse: A Children’s Oncology Group Study (Pog 8866)

摘要

Administration of L-asparaginase is limited by hypersensitivity reactions mediated by anti-asparaginase antibodies. To overcome this problem, native E. coli L-asparaginase was conjugated to polyethylene glycol to formulate PEG-L-asparaginase, a preparation with decreased immunogenicity and increased circulating half-life. In early trials, PEG-L-asparaginase was tolerated by patients known to be hypersensitive to the native E. coli product. Between 1988-1992, the Pediatric Oncology Group (POG) conducted a Phase II, randomized trial to compare the efficacy and toxicity of PEG-L-asparaginase compared to native E. coli asparaginase in a standard reinduction regimen for children with acute lymphoblastic leukemia in second bone marrow relapse.MethodsAll patients (n=76) received standard doses of vincristine and prednisone. Non-hypersensitive patients (n = 34) were randomized to receive either PEG-L-asparaginase 2,500 IU/m²/dose intramuscularly on days 1 and 15 (Treatment I) or native E. coli asparaginase 10,000 IU/m²/dose intramuscularly on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 (Treatment II). Patients with a clinical history of an allergic reaction to unmodified asparaginase were directly assigned to treatment with PEG-L-asparaginase (n = 42). Asparaginase levels and anti-asparaginase antibody titers were monitored in all patients. Response and toxicity were scored using conventional criteria.