AMSA: in vivo log cell kill for leukemic clonogenic cells versus toxicity for normal hemopoietic stem cells in a rat model for human acute myelocytic leukemia (BNML).

The efficacy of AMSA was evaluated quantitatively in a rat model (BNML) relevant for human acute myelocytic leukemia. The LD50 values observed in normal and leukemic Brown-Norway rats were 26.4 and 28.3 mg/kg respectively. In the higher dose ranges, the major cause of death was acute cardio-pulmonary toxicity. After single dose treatment, 20 mg AMSA/kg resulted in a surviving fraction of 5.5 X 10(2) for normal pluripotent hemopoietic stem cells and 4.1 X 10(-5) for in vivo clonogenic leukemic cells. With repeated administration of the drug amounting to the same total dose, even a 4 log difference in cell kill was observed between both cell populations. These studies provide quantitative information on the therapeutic index of AMSA and support the inclusion of this drug in first-line treatment regimens for acute myelocytic leukemia.