Millar B C, Bell J B, Maitland J A, Zuiable A, Gore M E, Selby P J, McElwain T J
Section of Medicine, Institute of Cancer Research, Sutton, Surrey.
Br J Haematol. 1989 Feb;71(2):213-22. doi: 10.1111/j.1365-2141.1989.tb04257.x.
Myeloma colonies (MY-CFUc) from 7/24 patients undergoing treatment with VAMP (vincristine, adriamycin and methyl prednisolone) and high dose melphalan (HDM) were melphalan-resistant. It was not possible to conclude that VAMP induced melphalan resistance in MY-CFUc, but that resistance is endogenous in some myeloma cell populations. In 12/13 of the same patients of whom four had MY-CFUc which were melphalan resistant, the sensitivity of MY-CFUc and GM-CFUc to busulphan was similar. Thus resistance of MY-CFUc to melphalan did not confer resistance to busulphan. MY-CFUc from 1/7 of a second group of patients were adriamycin-resistant. This resistance was removed when the cells were treated with a combination of verapamil (3 micrograms/ml) and adriamycin. Verapamil also enhanced the toxicity of adriamycin to MY-CFUc from two patients where there was no evidence for adriamycin resistance. In these three patients the sensitivity of both MY-CFUc and GM-CFUc was similar after treatment with verapamil. Verapamil did not affect the uptake or efflux of 3H-daunorubicin in sensitive and resistant RPMI-8226 cells (myeloma) and peripheral blood mononuclear cells from a normal donor; neither did it affect the binding of 3H-daunorubicin to nucleic acid. It is concluded that verapamil may be a useful adjuvant to VAMP chemotherapy and that busulphan may provide an alternative to melphalan in patients whose myeloma cells are melphalan resistant.
接受VAMP（长春新碱、阿霉素和甲基强的松龙）及大剂量美法仑（HDM）治疗的24例患者中有7例的骨髓瘤集落（MY - CFUc）对美法仑耐药。无法得出VAMP诱导MY - CFUc对美法仑耐药的结论，但这种耐药性在某些骨髓瘤细胞群体中是内源性的。在同一批13例患者中的12例中（其中4例的MY - CFUc对美法仑耐药），MY - CFUc和粒细胞 - 巨噬细胞集落形成单位（GM - CFUc）对白消安的敏感性相似。因此，MY - CFUc对美法仑的耐药性并未导致对白消安的耐药。第二组患者中有1/7的MY - CFUc对阿霉素耐药。当用维拉帕米（3微克/毫升）和阿霉素联合处理细胞时，这种耐药性被消除。维拉帕米还增强了阿霉素对另外2例无阿霉素耐药证据患者的MY - CFUc的毒性。在这3例患者中，用维拉帕米处理后，MY - CFUc和GM - CFUc的敏感性相似。维拉帕米不影响敏感和耐药的RPMI - 8226细胞（骨髓瘤细胞）及正常供体外周血单个核细胞对3H - 柔红霉素的摄取或流出；它也不影响3H - 柔红霉素与核酸的结合。得出的结论是，维拉帕米可能是VAMP化疗的一种有用辅助药物，对于骨髓瘤细胞对美法仑耐药的患者，白消安可能是美法仑的一种替代药物。
