PEG-Asparaginase Allergy in Children With Acute Lymphoblastic Leukemia in the NOPHO ALL2008 Protocol

BackgroundL-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. ProcedureChildren (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 (R)) 1,000 IU/m(2)/dose administered at 2 or 6 weeks intervals during a total period of 30 weeks. ( no: NCT00819351). ResultsOf 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 2hr after PEG-asparaginase administration and ranged from mild symptoms to systemic anaphylaxis. Nine patients experienced an anaphylactic reaction within 1hr and 50min from asparaginase administration; none were fatal. Four of 68 patients (6%) who subsequently received Erwinase therapy also reacted allergic to Erwinase. ConclusionClinical allergy to PEG-asparaginase occurred early in treatment, was in general moderate in severity, and mostly developed within 2hr after PEG-asparaginase administration. The risk of subsequent Erwinase allergic reactions was low. Pediatr Blood Cancer 2015;62:427-433. (c) 2014 Wiley Periodicals, Inc.