Impact of Clinical and Subclinical Hypersensitivity to Asparaginase in Acute Lymphoblastic Leukemia

Abstract

Asparaginase is an essential element of acute lymphoblastic leukemia treatment. It depletes serum asparagine (an amino acid necessary for synthesis of cellular proteins), deprives leukemic blast cells of asparagine, and eventually results in cell death. To gain benefit from asparaginase, asparagine depletion must be ensured by giving intensive therapy and completing the full course of treatment. Three formulations of asparaginase exist; two are derived from Escherichia coli, a native form and pegylated form, and one is derived from Erwinia chrysanthemi (Erwinia asparaginase). Like many large proteins, asparaginases are immunogenic, and some patients develop antibodies to asparaginase. Antibodies may result in clinical hypersensitivity or subclinical hypersensitivity without symptoms, and both can result in a reduction in asparaginase activity and may affect therapeutic benefit. Clinical hypersensitivity is the most common reason for patients to stop asparaginase treatment. Subclinical hypersensitivity can only be identified by laboratory testing; therapeutic monitoring of asparaginase activity is used as a surrogate measure for asparagine depletion.