The Impact of L-Asparaginase Hypersensitivity and Desensitization in Children with Acute Lymphoblastic Leukemia.
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INTRODUCTION: L-asparaginase is a key chemotherapeutic component of acute lymphoblastic leukemia (ALL) regimens. When hypersensitivity reactions (HSRs) occur, limited availability of alternative L-asparaginase preparations can jeopardize adherence to intended chemotherapy protocols. The aim of this study was to assess the impact of L-asparaginase-related hypersensitivity and subsequent desensitization on survival outcomes in patients with ALL. METHODS: Children with ALL treated according to the modified St. Jude Total XIII protocol between January 1997 and December 2007 who experienced systemic HSRs to L-asparaginase were included in the study. Recorded variables included demographics, ALL characteristics, event-free survival, desensitization procedure, and premedication regimens. RESULTS: Of 221 children with ALL (65.2% male; median age at diagnosis 6.11 years [3.2-9.1]), L-asparaginase HSR rate was 12.6%, including 19 (67.8%) cases of anaphylaxis. Concomitant drug allergies were reported to methotrexate (n = 2), etoposide (n = 2), and daunomycin (n = 1). HSRs were most frequent during remission induction (50%) and least during maintenance (10.7%). Desensitization to asparaginase was performed in 15 patients; others received premedication (n = 5) or E. coli asparaginase was discontinued according to the protocol and replaced with Erwinia or polyethylene glycol (PEG)-asparaginase (n = 8). Among the 190 patients with long-term follow-up, 10-year overall survival was lower in the L-asparaginase-allergic group than in nonallergic patients (20/26, 76.9% vs. 149/164, 90.9%; p = 0.035). In the desensitization group (n = 13), the overall survival rates at five and 10 years were 92.3% and 69%, respectively, while in the no desensitization group (n = 13), the rates were 92.3% and 84.6%, respectively (p > 0.05). CONCLUSION: In this cohort of pediatric patients with ALL, desensitization to L-asparaginase was not associated with a statistically significant difference in prognosis.