Gulati S C, Atzpodien J, Langleben A, Shimazaki C, Jain K, Yopp J, Ng R P, Colvin O M, Clarkson B D
Laboratory of Hematopoietic Cell Kinetics, Memorial Sloan-Kettering Cancer Center, New York.
Acta Haematol. 1988;80(2):65-70. doi: 10.1159/000205604.
The success of autologous bone marrow transplantation for B cell lymphoma may depend on the efficacy of in vitro purification of patients' tumor cell-contaminated marrow. In this study, we tested the toxicity of seven different chemotherapeutic agents against two B cell lymphoma lines (LY-16 and SK-DHL-2) as compared to normal human bone marrow granulocyte-macrophage progenitor cells (CFU-GM). 4-Hydroperoxycyclophosphamide (4-HC), VP-16-213 (VP-16), nitrogen mustard, and vincristine showed a highly selective toxicity against cultured lymphoma cells; i.e., at doses sufficient to induce a 4-log clonogenic tumor cell reduction (4-HC 21 micrograms/ml, VP-16 50 micrograms/ml, nitrogen mustard and vincristine 5 micrograms/ml), 10.0 +/- 6.7, 3.0 +/- 3.2, 23.2 +/- 22.7 and 24.0 +/- 17.0% (mean +/- 1 SD), respectively, of normal bone marrow CFU-GM were preserved. The differential sensitivity of tumor cells and normal hematopoietic precursors was less prominent after exposure of cells to cis-diamminechloroplatinum II (cis-platinum); thus, at a drug dose of 100 micrograms/ml, all detectable lymphoma cells could be eradicated (i.e., greater than or equal to 4 log reduction) while a CFU-GM recovery of only 0.2 +/- 0.2% was observed. In contrast, adriamycin and bleomycin, at the highest tumoricidal concentrations tested (5 and 100 micrograms/ml, respectively) did not exhibit a selective toxicity toward lymphoma cell lines. In summary, our results suggest that nitrogen mustard and vincristine, as well as 4-HC and VP-16, may be useful agents for the ex vivo treatment of bone marrow grafts form B cell lymphoma patients.
自体骨髓移植治疗B细胞淋巴瘤的成功可能取决于体外净化患者肿瘤细胞污染骨髓的效果。在本研究中，我们测试了七种不同化疗药物对两种B细胞淋巴瘤细胞系（LY-16和SK-DHL-2）的毒性，并与正常人骨髓粒-巨噬细胞祖细胞（CFU-GM）进行比较。4-氢过氧环磷酰胺（4-HC）、依托泊苷（VP-16）、氮芥和长春新碱对培养的淋巴瘤细胞显示出高度选择性毒性；即，在足以诱导肿瘤细胞克隆形成减少4个对数级的剂量下（4-HC 21微克/毫升、VP-16 50微克/毫升、氮芥和长春新碱5微克/毫升），分别有10.0±6.7%、3.0±3.2%、23.2±22.7%和24.0±17.0%（平均值±1标准差）的正常骨髓CFU-GM得以保留。细胞暴露于顺二氯二氨铂（顺铂）后，肿瘤细胞与正常造血前体细胞的差异敏感性不那么明显；因此，在药物剂量为100微克/毫升时，所有可检测到的淋巴瘤细胞均可被根除（即减少大于或等于4个对数级），而观察到CFU-GM的回收率仅为0.2±0.2%。相比之下，阿霉素和博来霉素在测试的最高杀肿瘤浓度下（分别为5和100微克/毫升）对淋巴瘤细胞系未表现出选择性毒性。总之，我们的结果表明，氮芥和长春新碱以及4-HC和VP-16可能是用于体外处理B细胞淋巴瘤患者骨髓移植物的有用药物。
