Hagenbeek A, Martens A C
Leuk Res. 1985;9(11):1389-95. doi: 10.1016/0145-2126(85)90127-4.
To evaluate in quantitative terms the contribution of leukemic cells present in the autologous marrow graft to the occurrence of leukemia relapse after autologous bone marrow transplantation, preclinical studies were performed in a rat model for human acute myelocytic leukemia (BNML). Firstly, the number of leukemic cells which--after intravenous transfer--cause death from leukemia in 50% of the recipient rats proved to be 24.7 cells. Secondly, it appeared that the regrowth of leukemic cells in rats heavily pretreated with high-dose cyclophosphamide and total body irradiation was significantly hampered as compared with non-pretreated controls as judged by survival times (37 and 31 days, respectively after 10(3) BNML cells i.v.). The most likely explanation is treatment-induced damage to the microenvironment. Differences in patterns of lodging of infused leukemic cells were ruled out by comparing the uptake of 51Cr-labeled BNML cells in various organs. Finally, extrapolated from the available rat data on log leukemic cell kill induced by high-dose chemoradiotherapy, an hypothesis is presented relating the total tumor load in man to the clinical outcome of autologous bone marrow transplantation. From this hypothesis it is derived that the minimal number of leukemic cells that causes leukemia upon intravenous transfer varies between 10(4) and 10(6).
为了定量评估自体骨髓移植中存在的白血病细胞对自体骨髓移植后白血病复发的影响，我们在人类急性髓细胞白血病（BNML）的大鼠模型中进行了临床前研究。首先，经静脉注射后能导致50%的受体大鼠死于白血病的白血病细胞数量为24.7个。其次，与未预处理的对照组相比，经高剂量环磷酰胺和全身照射预处理的大鼠中白血病细胞的再生长明显受到阻碍，这一点通过生存时间来判断（静脉注射10³个BNML细胞后，分别为37天和31天）。最可能的解释是治疗引起的微环境损伤。通过比较51Cr标记的BNML细胞在各个器官中的摄取情况，排除了注入的白血病细胞在着床模式上的差异。最后，根据现有的大鼠数据外推高剂量放化疗诱导的对数白血病细胞杀伤情况，提出了一个关于人类总肿瘤负荷与自体骨髓移植临床结果关系的假说。从这个假说可以推断，经静脉注射后能引发白血病的白血病细胞最小数量在10⁴到10⁶之间。
