• Lynda M Vrooman, Jeffrey G Supko, Donna S Neuberg, Barbara L Asselin, Uma H Athale, Luis Clavell, Kara M Kelly, Caroline Laverdière, Bruno Michon, Marshall Schorin, Harvey J Cohen, Stephen E Sallan, and Lewis B Silverman.
• Department of Pediatric Oncology, Biostatistics, and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. lynda_vrooman@dfci.harvard.edu
• Pediatr Blood Cancer. 2010 Feb 1; 54 (2): 199-205.

BackgroundEscherichia 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.Patients And MethodsBetween 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.ResultsForty-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).ConclusionsTwice-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.(c) 2009 Wiley-Liss, Inc.

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