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).

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: Administration of L-asparaginase is limited by hypersensitivity reactions mediated by anti-asparaginase antibodies. To overcome this problem, native Escherichia coli L-asparaginase was conjugated to polyethylene glycol (PEG) 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. METHODS: The Pediatric Oncology Group conducted a phase II, randomized trial to compare the efficacy and toxicity of PEG-L-asparaginase compared with native E. coli asparaginase in children with acute lymphoblastic leukemia in second bone marrow relapse. All patients (n=76) received standard doses of vincristine and prednisone. Nonhypersensitive patients (n=34) were randomized to receive either PEG-L-asparaginase of 2500 IU/m/dose intramuscularly on days 1 and 15 (treatment I) or native E. coli asparaginase of 10,000 IU/m/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. RESULTS: The complete response rate for the total study population was 41%. There was no difference in complete response between patients randomized to PEG (47%) and native asparaginase (41%). PEG was well tolerated even in patients with prior allergic reactions to native asparaginase. PEG half-life was shorter in patients with prior allergy. CONCLUSIONS: PEG asparaginase is a useful agent in patients with allergic reactions to native asparaginase.

Full Text

Duke Authors

Cited Authors

  • Kurtzberg, J; Asselin, B; Bernstein, M; Buchanan, GR; Pollock, BH; Camitta, BM

Published Date

  • December 2011

Published In

Volume / Issue

  • 33 / 8

Start / End Page

  • 610 - 616

PubMed ID

  • 22042277

Pubmed Central ID

  • PMC3557823

Electronic International Standard Serial Number (EISSN)

  • 1536-3678

Digital Object Identifier (DOI)

  • 10.1097/MPH.0b013e31822d4d4e


  • eng

Conference Location

  • United States