Incidence and management of asparaginase-associated adverse events in patients with acute lymphoblastic leukemia.
Asparaginase is an enzyme that breaks down extracellular asparagine into aspartic acid and ammonia. Depletion of extracellular asparagine inhibits the growth of lymphocytic leukemic cells. Unlike normal cells, lymphoblasts lack the enzyme to synthesize asparagine and therefore rely on an exogenous source of this amino acid to maintain cellular protein synthesis. Asparagine depletion results in nutritional deprivation, inhibition of protein synthesis, and subsequent apoptotic cell death in lymphoblasts. Asparaginase therapy is an essential component of the treatment protocol for acute lymphoblastic leukemia. The effect of asparaginase on protein synthesis may result in a number of toxicities, including thrombosis, pancreatitis, hyperglycemia, and hepatotoxicity. This review discusses the incidence of asparaginase-related adverse events, compares available asparaginase formulations with respect to the emergence of certain toxicities, and considers management strategies for these toxicities in patients with acute lymphoblastic leukemia.
Earl
Marc
M
Cleveland Clinic, Department of Pharmacy, 9500 Euclid Avenue/JJN1-02, Cleveland, OH 44195, USA. earlm@ccf.org
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects*; D001778:Blood Coagulation Disorders / Q000139:chemically induced; D002648:Child; D004342:Drug Hypersensitivity / Q000209:etiology; D006801:Humans; D015994:Incidence; D008099:Liver / Q000187:drug effects; D010195:Pancreatitis / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D000970:Antineoplastic Agents; D001215:Asparaginase