Fludarabine Phosphate (NSC 312878) Infusions for the Treatment of Acute Leukemia: Phase I and Neuropathological Study

摘要: Fludarabine phosphate (NSC 312878), an adenosine deaminase resistant analogue of 9-beta-D-arabinofuranosyladenine, has entered clinical trials. Eleven patients with acute leukemia in relapse received 14 courses fludarabine as a 5-day continuous infusion administered at doses 40 to 100 mg/m2/day. Toxicity was characterized by uniform myelosuppression, well occasional nausea, vomiting, and hepatotoxicity. Three episodes metabolic acidosis lactic acidemia were noted. In addition, three suffered neurotoxicity. Two these had severe neurotoxicity syndrome blindness, encephalopathy, coma. Neither patient recovered neurological function. Neuropathological findings autopsy diffuse, necrotizing leukoencephalopathy which most the occipital lobes. The medullary pyramids posterior columns also severely affected. This sporadic fatal observed only greater than maximum tolerated dose for is thus