Erwinia asparaginase is antigenically distinct from E.coli-derived asparaginase and may be used after E.coli-derived asparaginase hypersensitivity. In a single-arm, multicenter study, we evaluated nadir serum asparaginase activity (NSAA) and toxicity with intravenously administered asparaginase Erwinia chrysanthemi (IV-Erwinia) in children and adolescents with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma with hypersensitivity to E.coli-derived asparaginase.Patients and Methods.
Between 2012 and 2013, 30 patients (age 1–17 years) enrolled from 10 centers. Patients received IV-Erwinia, 25,000 IU/m2/dose on Monday/Wednesday/Friday, for 2 consecutive-weeks (6 doses = 1 cycle) for each dose of pegaspargase remaining in the original treatment plan. The primary objective was to determine the proportion of patients achieving NSAA ≥0.1 IU/ml 48 hr after dose 5 in Cycle 1. Secondary objectives included determining the proportion achieving NSAA ≥0.1 IU/ml 72 hr after Cycle 1 dose 6, and the frequency of asparaginase-related toxicities.Results.
Twenty-six patients completed Cycle 1; 24 were evaluable for NSAA assessment. In Cycle 1, NSAA ≥0.10 IU/ml was detected in 83% of patients (95% confidence interval [CI], 63–95%) 48 hr post-dose 5 (mean ± SD; 0.32 IU/ml ± 0.23), and in 43% (95% CI, 22–66%) 72 hr post-dose 6 (mean ± SD; 0.089 IU/ml ± 0.072). For all 30 patients over all cycles, hypersensitivity/infusional reactions with IV-Erwinia occurred in 37%, pancreatitis 7%, and thrombosis 3%.Conclusions.
IV-Erwinia administration in children/adolescents appeared feasible and tolerable. A therapeutically-effective NSAA (≥0.10 IU/ml) was achieved in most patients at 48 hr, but in fewer than half 72 hr post-dosing, suggesting that monitoring NSAA levels and/or every 48 hr dosing may be indicated. Pediatr Blood Cancer 2015. © 2015 Wiley Periodicals, Inc.