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)

Joanne Kurtzberg, Barbara Asselin, Mark Bernstein, George R. Buchanan, Brad H. Pollock, Bruce M. Camitta

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)610-616
Number of pages7
JournalJournal of Pediatric Hematology/Oncology
Volume33
Issue number8
DOIs
StatePublished - Dec 2011

Keywords

  • asparaginase
  • hypersensitivity
  • reinduction chemotherapy
  • relapsed acute lymphoblastic leukemia (ALL)

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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