Faculty Collaboration Database

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). J Pediatr Hematol Oncol 2011 Dec;33(8):610-6

Date

11/02/2011

Pubmed ID

22042277

Pubmed Central ID

PMC3557823

DOI

10.1097/MPH.0b013e31822d4d4e

Scopus ID

2-s2.0-80455158077 (requires institutional sign-in at Scopus site)   48 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.

Author List

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

MESH terms used to index this publication - Major topics in bold

Adolescent
Antibodies
Antineoplastic Combined Chemotherapy Protocols
Asparaginase
Bone Marrow
Child
Child, Preschool
Drug Hypersensitivity
Escherichia coli Proteins
Female
Humans
Infant
Male
Polyethylene Glycols
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prednisone
Recurrence
Treatment Outcome
Vincristine