Hagenbeek A, Martens A C
Eur J Cancer Clin Oncol. 1986 Oct;22(10):1255-8. doi: 10.1016/0277-5379(86)90328-7.
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.
在与人类急性髓细胞白血病相关的大鼠模型（BNML）中对AMSA的疗效进行了定量评估。正常和患白血病的棕色挪威大鼠的半数致死剂量（LD50）值分别为26.4和28.3毫克/千克。在较高剂量范围内，死亡的主要原因是急性心肺毒性。单剂量治疗后，20毫克AMSA/千克导致正常多能造血干细胞的存活分数为5.5×10²，体内克隆性白血病细胞的存活分数为4.1×10⁻⁵。当重复给药达到相同总剂量时，两个细胞群体之间甚至观察到4个对数级的细胞杀伤差异。这些研究提供了关于AMSA治疗指数的定量信息，并支持将该药物纳入急性髓细胞白血病的一线治疗方案。
