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Asparaginase in Acute Lymphoblastic Leukemia

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Asparaginase is an enzyme that has been historically derived from the E. coli bacteria and used as a short-acting medication in the treatment of acute lymphoblastic leukemia (ALL), explains Dan Douer, MD. The native form of E. coli derived asparaginase is no longer available in the United States, but an even shorter-acting formulation made from Erwina bacteria remains available, Douer notes.

Native E. Coli asparaginase was replaced by pegylated (PEG) asparaginase. In a randomized clinical trial, a single dose of induction therapy with PEG-asparaginase plus vincristine and prednisone was found to have similar activity and toxicity as 9 doses of native asparaginase. Additionally, pegylation decreased the risk of developing hypersensitivity reactions and neutralizing antibodies, Douer notes.

PEG-asparaginase is a critical drug that is used in every pediatric protocol, notes Douer. However, liver toxicity, which occurs in 30% of patients, can limit the utility of the agent. Data have shown that although the liver recovers, the toxicity is common after the first cycle and can delay the next cycle of treatment.

As patients with ALL get older, side effects associated with PEG-asparaginase increase, primarily hyperbilirubinemia, Mark R. Litzow, MD, mentions. Strategies to reduce toxicity include separating the administration of PEG-asparaginase from other myelosuppressive therapies, such as daunorubicin. Additionally, PEG-asparaginase can be combined with other chemotherapies and assays are available to measure asparaginase levels, in order to predict response.

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