title: Allergic reactions and antiasparaginase antibodies in children with high-risk acute lymphoblastic leukemia: A children's oncology group report.
abstract: BACKGROUND
  The objectives of this study were to assess the incidence of clinical allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children with high-risk acute lymphoblastic leukemia treated with pegylated (PEG) Escherichia coli ASNase and to determine whether they carry any prognostic significance.
  
  
  METHODS
  Of 2057 eligible patients, 1155 were allocated to augmented arms in which PEG ASNase replaced native ASNase postinduction. Erwinia chrysanthemi (Erwinia) ASNase could be used to replace native ASNase after allergy, if available. Allergy and survival data were complete for 990 patients. End-induction antibody titers were available for 600 patients.
  
  
  RESULTS
  During the consolidation phase, 289 of 990 patients (29.2%) had an allergic reaction. There were fewer allergic reactions to Erwinia ASNase than to native ASNase (odds ratio, 4.33; P < .0001) or PEG ASNase (odds ratio, 3.08; P < .0001) only during phase 1 of interim maintenance. There was no significant difference in 5-year event-free survival (EFS) between patients who received PEG ASNase throughout the entire study postinduction versus those who developed an allergic reaction to PEG ASNase during consolidation phase and subsequently received Erwinia ASNase (80.8% ± 2.8% and 81.6% ± 3.8%, respectively; P = .66). Patients who had positive antibody titers postinduction were more likely to have an allergic reaction to PEG ASNase (odds ratio, 2.4; P < .001). The 5-year EFS rate between patients who had negative versus positive antibody titers (80% ± 2.6% and 77.7% ± 4.3%, respectively; P = .68) and between patients who did not receive any ASNase postconsolidation and those who received PEG ASNase throughout the study (P = .22) were significantly different.
  
  
  CONCLUSIONS
  The current results demonstrate differences in the incidence rates of toxicity between ASNase preparations but not in EFS. The presence of anti-ASNase antibodies did not affect EFS.
authors: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Richard H
authors: RH
authors: Ko
authors: Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
authors: Tamekia L
authors: TL
authors: Jones
authors: State University of New York of New York Downstate Medical Center, Brooklyn New York.
authors: David
authors: D
authors: Radvinsky
authors: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Nathan
authors: N
authors: Robison
authors: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Paul S
authors: PS
authors: Gaynon
authors: Division of Pediatric Hematology and Oncology, Harbor-University of California Los Angeles Medical Center, Torrance, California.
authors: Eduard H
authors: EH
authors: Panosyan
authors: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.
authors: Ioannis A
authors: IA
authors: Avramis
authors: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Vassilios I
authors: VI
authors: Avramis
authors: Department of Pediatrics, St. Peter's University Hospital, New Brunswick, New Jersey.
authors: Joan
authors: J
authors: Rubin
authors: Children's Oncology Group, Monrovia, California.
authors: Lawrence J
authors: LJ
authors: Ettinger
authors: Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland.
authors: Nita L
authors: NL
authors: Seibel
authors: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Girish
authors: G
authors: Dhall
mesh_terms: D000906:Antibodies / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology; D001215:Asparaginase / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016974:Dickeya chrysanthemi / Q000201:enzymology / Q000276:immunology; D004342:Drug Hypersensitivity / Q000453:epidemiology* / Q000276:immunology; D004926:Escherichia coli / Q000201:enzymology / Q000276:immunology; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D011092:Polyethylene Glycols / Q000737:chemistry; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D001215:Asparaginase
keywords: asparaginase; childhood acute lymphoblastic leukemia; drug hypersensitivity; survival