EFFICACY OF PIPERAZINEDIONE PRIOR TO BONE-MARROW TRANSPLANTATION - STUDIES IN A RAT MODEL FOR HUMAN ACUTE MYELOCYTIC-LEUKEMIA

Abstract

The efficacy and toxicity of piperazinedione were investigated in a Brown Norway rat model for acute myelocytic leukemia (BNML). Treatment was started at a stage which is comparable to a full-blown relapse in human patients. Early toxicity-induced deaths due to the very strong myelosuppressive effect of the drug could be prevented by bone marrow transplantation followed by repeated blood transfusions. With a total dose of 16 mg/kg (human dose, 85 mg/m2), death caused by GI [gastrointestinal] tract and lung damage was inevitable. As judged by prolongation of survival, at the most a 9-log cell-kill was achieved. No cures were obtained, since the total tumor load at the start of treatment was > 109 cells (.apprx. 5 .times. 109). The possible presence of drug-resistant cells was not excluded. No significant differences in efficacy were found between daily push treatment and split daily doses using total doses of 10-12 mg/kg.