Psychiatric symptoms associated with L-asparaginase administration

Abstract

THE ENZYME, L-asparaginase, (L-asparagine amidohydrolase, E. C.3.5.1 .l.) isolated from Escherichia COZ~,~*~ is effective in producing remissions in patients with acute leukemia.3*4 Toxic side effects reported during clinical trials with L-asparaginase have included fever and chills, azotemia, pancreatitis, hyperglycemia, allergic reactions and hepatic injury characterized by hypoalbuminemia, hypofibrinogenemia and fatty metamorphosis. 5s These reports have also noted profound mental symptoms suggestive of central nervous system toxicity.5s The psychiatric symptoms described were depression, ranging from mild to severe, lethargy, confusion, delirium, fugue states, and a delirium-tremens-like state.5* These mental symptoms were noted to occur less frequently in children59 ** s Slowing of electroencephalographic tracings in these patients has been reported. ‘* * This communication describes the psychiatric symptoms seen during a clinical trial of L-asparaginase in adult patients with acute leukemia. The possible relationship of psychiatric symptoms to central nervous system dysfunction as a part of generalized impairment of protein synthesis is explored.