L-Asparaginase: Clinical, Biochemical, Pharmacological, and Immunological Studies

Abstract

Forty patients with acute leukemia were treated with Intravenous L-asparaginase in doses ranging from 10 to 1,000 international units/kg body weight per day for 2 to 20 days. Most had long-standing disease and had exhausted conventional therapy. The remission rate appeared to be unaffected by dose, schedule, or previous chemotherapy. There was a 66% response rate for acute lymphoblastic leukemia and an approximately 12% response rate for nonlymphocytic leukemia. Second and third remissions were obtained. Toxicity was not strictly dose related and consisted of fever, anorexia, nausea, vomiting, decreased protein synthesis, biochemical hepatic dysfunction, elevated blood ammonia, nonketotic hyperglycemia, and anaphylaxis. Although there were two deaths directly attributed to L-asparaginase, most patients tolerated the enzyme well with very little impairment of performance status. The rapid clearance of plasma enzyme and the development of passive hemagglutinating and reagin types of antibodies are correlated with the development of anaphylaxis. The relationship of plasma L-asparagine to disease status is discussed.