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, Bradley H Pollock, Bruce M. Camitta

Research output: Contribution to journalArticle

34 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Asparaginase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Bone Marrow
Recurrence
Hypersensitivity
Escherichia coli
Half-Life
Anti-Idiotypic Antibodies

Keywords

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

ASJC Scopus subject areas

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

Cite this

@article{a359ab1ed1a1466e8ef0d9918e5d14a8,
title = "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)",
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.",
keywords = "asparaginase, hypersensitivity, reinduction chemotherapy, relapsed acute lymphoblastic leukemia (ALL)",
author = "Joanne Kurtzberg and Barbara Asselin and Mark Bernstein and Buchanan, {George R.} and Pollock, {Bradley H} and Camitta, {Bruce M.}",
year = "2011",
month = "12",
doi = "10.1097/MPH.0b013e31822d4d4e",
language = "English (US)",
volume = "33",
pages = "610--616",
journal = "Journal of Pediatric Hematology/Oncology",
issn = "1077-4114",
publisher = "Lippincott Williams and Wilkins",
number = "8",

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TY - JOUR

T1 - 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

T2 - A children's Oncology Group Study (POG 8866)

AU - Kurtzberg, Joanne

AU - Asselin, Barbara

AU - Bernstein, Mark

AU - Buchanan, George R.

AU - Pollock, Bradley H

AU - Camitta, Bruce M.

PY - 2011/12

Y1 - 2011/12

N2 - 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.

AB - 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.

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KW - hypersensitivity

KW - reinduction chemotherapy

KW - relapsed acute lymphoblastic leukemia (ALL)

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