Toxicity of L-asparaginase in children with advanced leukemia

Abstract

A total of 105 patients with advanced acute leukemia in relapse received 123 trials of L-asparaginase. Three different schedules were used, two of which involved simultaneous administration of vincristine and prednisone. Treatment was temporarily interrupted because of toxicity in 14 patients, and permanently discontinued in an additional 31. In 13 patients, this occurred before 10 doses of L-asparaginase were given, while in the remaining 18 patients, therapy was stopped after remission was attained. The major toxicities were pancreatitis (fatal in four patients), hypersensitivity reactions, disturbances of liver function (fatal in two patients), and clinical and laboratory manifestations of central nervous system (CNS) dysfunction. Diabetic keto-acidosis was encountered in two patients and was fatal in one. Severe leukopenia ascribed to L-asparaginase occurred in two patients, in one of whom it was the contributory cause of death. Toxicity was not clearly different with any of the three treatment schedules. Most of the patients with only laboratory evidence of toxicity had no associated clinical manifestations, and this did not appear to decrease the likelihood of obtaining a remission.