Hypersensitivity Reactions to Asparaginase Therapy in Acute Lymphoblastic Leukemia: Immunology and Clinical Consequences

Asparaginase is commonly used in combination therapy of acute lymphoblastic leukemia. However, as an immunogenic protein, hypersensitivity reactions (HSRs) during asparaginase therapy are frequent, indicating the development of anti-asparaginase antibodies. These can be associated with diminished clinical effectiveness, including poorer survival. Therapeutic drug monitoring of serum asparaginase activity to confirm complete asparagine depletion is therefore crucial during asparaginase therapy. Switching to alternative types of asparaginase is recommended for patients experiencing HSRs or silent inactivation; those with HSRs or silent inactivation on derived asparaginases should switch to another preparation. However, prior global shortages of asparaginase highlight the importance of alternative non- derived asparaginase, including recombinant asparaginase.