title: PEG-asparaginase allergy in children with acute lymphoblastic leukemia in the NOPHO ALL2008 protocol.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Louise Tram
authors.initials: LT
authors.lastname: Henriksen
authors.forename: Arja
authors.initials: A
authors.lastname: Harila-Saari
authors.forename: Ellen
authors.initials: E
authors.lastname: Ruud
authors.forename: Jonas
authors.initials: J
authors.lastname: Abrahamsson
authors.forename: Kaie
authors.initials: K
authors.lastname: Pruunsild
authors.forename: Goda
authors.initials: G
authors.lastname: Vaitkeviciene
authors.forename: Ólafur Gísli
authors.initials: ÓG
authors.lastname: Jónsson
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
authors.forename: Mats
authors.initials: M
authors.lastname: Heyman
authors.forename: Henrik
authors.initials: H
authors.lastname: Schrøder
authors.forename: Birgitte Klug
authors.initials: BK
authors.lastname: Albertsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000707:Anaphylaxis / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase
keywords: acute lymphoblastic leukemia; allergy; asparaginase; children