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.
authors: Duke University Medical Center, Durham, NC, USA.
authors: Joanne
authors: J
authors: Kurtzberg
authors: Barbara
authors: B
authors: Asselin
authors: Mark
authors: M
authors: Bernstein
authors: George R
authors: GR
authors: Buchanan
authors: Brad H
authors: BH
authors: Pollock
authors: Bruce M
authors: BM
authors: Camitta
mesh_terms: D000293:Adolescent; D000906:Antibodies / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity / Q000209:etiology / Q000276:immunology; D029968:Escherichia coli Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000906:Antibodies; D029968:Escherichia coli Proteins; D011092:Polyethylene Glycols; D014750:Vincristine; D001215:Asparaginase; D011241:Prednisone