Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia

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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. Patients and 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/m2). 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 (≥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. Pediatr Blood Cancer 2010;54:199–205.
Funding Information
  • National Cancer Institute (5 P01CA068484)

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