Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli-Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia

作者：Vrooman Lynda M^*; Kirov Ivan I; Dreyer ZoAnn E; Kelly Michael; Hijiya Nobuko; Brown Patrick; Drachtman Richard A; Messinger Yoav H; Ritchey A Kim; Hale Gregory A; Maloney Kelly; Lu Yuan; Plourde Paul V; Silverman Lewis B

来源：Pediatric Blood and Cancer, 2016, 63(2): 228-233.

DOI：10.1002/pbc.25757

• acute lymphoblastic leukemia
• childhood ALL
• clinical trials
• Erwinia asparaginase
• pharmacokinetics

Background. 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/m(2)/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.

• 出版日期2016-2
• 单位西北大学