Asparaginase

Asparaginase is a therapeutic enzyme used in the treatment of certain cancers, most notably acute lymphoblastic leukemia (ALL). It works by catalyzing the hydrolysis of L-asparagine to L-aspartate and ammonia. Many ALL cells are unable to synthesize sufficient asparagine, so systemic depletion of circulating asparagine inhibits protein synthesis and induces cell death in malignant lymphoblasts while affecting normal cells less severely.

Origin and formulations: Commercial preparations include native L-asparaginase derived from Escherichia coli (and, in some cases, Erwinia chrysanthemi) and pegylated forms such as pegaspargase. Erwinia-derived asparaginase is used when reactions occur with E. coli–derived products. Pegylation increases the enzyme’s half-life, allowing less frequent dosing.

Administration: Asparaginase is given by intramuscular or intravenous injection. Dosing and scheduling vary by regimen and indication, with pegylated forms often administered less frequently due to their longer duration of action.

Clinical use: It is a standard component of multi-agent chemotherapy regimens for pediatric and adult ALL and is used in some lymphoid malignancies. Treatment plans typically combine asparaginase with other cytotoxic drugs and steroids.

Safety and adverse effects: Significant risks include hypersensitivity and anaphylaxis, pancreatitis, hepatotoxicity, and coagulation abnormalities (bleeding or thrombosis). Other possible effects include hyperglycemia, hyperbilirubinemia, dyslipidemia, mucositis, and neutropenia. Immunogenicity can limit use of non-pegylated forms; switching to an Erwinia-derived product is considered for allergic reactions. Monitoring of liver enzymes, pancreatic enzymes, and coagulation parameters is recommended during therapy.