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. 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.