title: Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia.
abstract: BACKGROUND
  Escherichia coli asparaginase is an important component of treatment for childhood acute lymphoblastic leukemia (ALL); however, hypersensitivity develops in up to 30% of patients. We assessed the nadir enzyme activity and tolerability of Erwinia asparaginase, an alternative preparation, in E. coli asparaginase-allergic patients.
  
  
  METHODS
  Between 2000 and 2002, 215 children with newly diagnosed ALL were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 00-01 and were to receive 30 weekly doses of intramuscular E. coli asparaginase. If E. coli asparaginase allergy developed, patients were switched to twice-weekly intramuscular Erwinia asparaginase (25,000 IU/m(2)). Nadir serum asparaginase activity (NSAA) was measured every 3 weeks.
  
  
  RESULTS
  Forty-two patients (20%) developed E. coli asparaginase allergy and switched to Erwinia. Of 38 patients with evaluable samples, 34 (89%) Erwinia-treated patients had at least one therapeutic NSAA (> or =0.1 IU/ml). The median NSAA was 0.247 IU/ml 3 days and 0.077 IU/ml 4 days after an Erwinia dose. Associated toxicities included allergy in 14 (33%) and pancreatitis in 3 patients (7%). At a median follow-up of 5.4 years, event-free survival (+/-standard error) of the 42 patients who switched to Erwinia was 86 +/- 5% compared with 81 +/- 3% for the 170 patients without E. coli asparaginase allergy (P = 0.55).
  
  
  CONCLUSIONS
  Twice-weekly Erwinia asparaginase was well tolerated and achieved a therapeutically effective NSAA in most E. coli asparaginase-allergic patients. Development of E. coli allergy and subsequent treatment with twice-weekly Erwinia did not adversely impact event-free survival. Erwinia asparaginase should be considered for E. coli asparaginase-allergic patients.
authors: Department of Pediatric Oncology, Biostatistics, and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. lynda_vrooman@dfci.harvard.edu
authors: Lynda M
authors: LM
authors: Vrooman
authors: Jeffrey G
authors: JG
authors: Supko
authors: Donna S
authors: DS
authors: Neuberg
authors: Barbara L
authors: BL
authors: Asselin
authors: Uma H
authors: UH
authors: Athale
authors: Luis
authors: L
authors: Clavell
authors: Kara M
authors: KM
authors: Kelly
authors: Caroline
authors: C
authors: Laverdière
authors: Bruno
authors: B
authors: Michon
authors: Marshall
authors: M
authors: Schorin
authors: Harvey J
authors: HJ
authors: Cohen
authors: Stephen E
authors: SE
authors: Sallan
authors: Lewis B
authors: LB
authors: Silverman
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001215:Asparaginase / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000517:prevention & control*; D004885:Erwinia / Q000201:enzymology*; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D007223:Infant; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase