PEG-asparaginase allergy in children with acute lymphoblastic leukemia in the NOPHO ALL2008 protocol

Pediatr Blood Cancer. 2015 Mar;62(3):427-33. doi: 10.1002/pbc.25319. Epub 2014 Nov 21.

Abstract

Background: L-Asparaginase is an effective drug in the treatment of childhood acute lymphoblastic leukemia (ALL). The use of L-asparaginase may be limited by serious adverse events of which allergy is the most frequent. The objective of this study was to describe the clinical aspects of PEG-asparaginase allergy in children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol.

Procedure: Children (1-17 years) enrolled in the NOPHO ALL2008 protocol between July 2008 and August 2011, who developed PEG-asparaginase allergy were identified through the NOPHO ALL2008 toxicity registry. In the NOPHO ALL2008 protocol, patients are randomized to 8 or 15 doses of intramuscular PEG-asparaginase (Oncaspar®) 1,000 IU/m(2) /dose administered at 2 or 6 weeks intervals during a total period of 30 weeks. (Clinical trials.gov no: NCT00819351).

Results: Of 615 evaluable patients, 79 patients developed clinical PEG-asparaginase allergy (cumulative risk; 13.2%) and discontinued PEG-asparaginase therapy for that reason. PEG-asparaginase allergy occurred after a median of two doses (75% range 2-4, max 14). In 58% of PEG-asparaginase hypersensitive patients, the clinical allergic reactions appeared within 2 hr after PEG-asparaginase administration and ranged from mild symptoms to systemic anaphylaxis. Nine patients experienced an anaphylactic reaction within 1 hr and 50 min from asparaginase administration; none were fatal. Four of 68 patients (6%) who subsequently received Erwinase therapy also reacted allergic to Erwinase.

Conclusion: Clinical allergy to PEG-asparaginase occurred early in treatment, was in general moderate in severity, and mostly developed within 2 hr after PEG-asparaginase administration. The risk of subsequent Erwinase allergic reactions was low.

Keywords: acute lymphoblastic leukemia; allergy; asparaginase; children.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anaphylaxis / chemically induced
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Asparaginase / administration & dosage*
  • Asparaginase / adverse effects
  • Child
  • Child, Preschool
  • Drug Hypersensitivity / etiology
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / adverse effects
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Risk Factors

Substances

  • Antineoplastic Agents
  • Polyethylene Glycols
  • pegaspargase
  • Asparaginase

Associated data

  • ClinicalTrials.gov/NCT00819351