The Impact of L-asparaginase Hypersensitivity and Desensitization in Children with Acute Lymphoblastic Leukemia

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.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 non-allergic 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 ten 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.