Efficacy of piperazinedione prior to bone marrow transplantation: studies in a rat model for human acute myelocytic leukemia.

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. However, with a total dose of 16 mg/kg (human dose, 85 mg/m2), death caused by GI tract and lung damage was inevitable. As judged by prolongation of survival, at the most of a 9-log cell-kill was achieved. No cures were obtained, since the total tumor load at the start of treatment was greater than 10(9) cells (about 5 X 10(9)). 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.