CYCLOPHOSPHAMIDE

Abstract

SUMMARY This report describes a series of investigations into the toxicity of cyclophosphamide in mice. It was found that chloroquine (three doses of 20 mg/kg) markedly increased cyclophosphamide toxicity. This occurred when the cyclophosphamide was given either as a single large dose (300–600 mg/kg) or in smaller daily doses (40 mg/kg). High dose prednisolone therapy (20 mg/kg/day for 8 days), but not low dose (5 mg/kg/day for 8 days), also increased the toxicity of cyclophosphamide. Three lethal syndromes related to cyclophosphamide administration were distinguished. (1) Acute toxic death followed a single large dose (600 mg/kg). (2) The same dose divided into two injections separated by 24 hr, or a lower single dose (400 mg/kg), led to death within 2 weeks, with the loss of circulating small lymphocytes. (3) Daily cyclophosphamide (40 mg/kg) led to profound bone marrow depression, superinfection, wasting, and death. Bone marrow transplantation was of value in the last two syndromes but was ineffective in altering the acute toxic deaths.