Morabito F, Messina G, Oliva B, Ramirez F, Callea V, Brugiatelli M, Nobile F
Department of Hematology, Ospedali Riuniti USSL 11, Reggio Calabria, Italy.
Haematologica. 1993 Jul-Aug;78(4):213-8.
Anthracycline-containing regimens have given controversial clinical results in CLL. Therefore, we explored the in vitro behavior of CLL B-cells after exposure to the compounds included in the most frequently used combination therapy regimen (CEOP).
A 4-day MTT colorimetric assay was used in vitro to test the effect of CEOP regimen drugs, either alone or in combination, on CLL B-cells. All drugs but mafosfamide, tested in place of cyclophosphamide, were used at concentrations corresponding to the in vivo dosage employed in the CEOP regimen. Chlorambucil was also studied since it represents the standard treatment for this disease.
Epirubicin, prednisone and vincristine displayed a cytotoxic effect in 15, 13 and 4 out of 30 samples, respectively. Combinations of the same drugs showed a synergistic effect in 6 out of 13 assays. A cytotoxic effect of chlorambucil was detected in 2 out of 5 responders to the combination of CEOP regimen drugs, and in 3 out of 7 non responders. Mafosfamide induced a reduction in cell survival in 60-80% of the samples, depending on its concentration.
The MTT assay is suitable for evaluating the in vitro chemosensitivity of CLL B-cells to multidrug regimen compounds. In the present study 40% of samples were resistant to CEOP regimen components in vitro. The possible role of MTT in predicting the clinical response to the CEOP regimen should still be established by prospective in vitro and in vivo studies.
含蒽环类药物的治疗方案在慢性淋巴细胞白血病（CLL）中取得了有争议的临床结果。因此，我们探讨了慢性淋巴细胞白血病B细胞在暴露于最常用联合治疗方案（CEOP）中的化合物后的体外行为。
采用4天MTT比色法在体外测试CEOP方案药物单独或联合使用对慢性淋巴细胞白血病B细胞的作用。除用马磷酰胺代替环磷酰胺进行测试外，所有药物均以与CEOP方案中体内用药剂量相对应的浓度使用。还对苯丁酸氮芥进行了研究，因为它是这种疾病的标准治疗药物。
表柔比星、泼尼松和长春新碱分别在30个样本中的15个、13个和4个样本中显示出细胞毒性作用。相同药物的组合在13次试验中的6次试验中显示出协同作用。在对CEOP方案药物组合有反应的5个样本中的2个以及7个无反应者中的3个中检测到苯丁酸氮芥的细胞毒性作用。马磷酰胺根据其浓度在60% - 80%的样本中诱导细胞存活率降低。
MTT试验适用于评估慢性淋巴细胞白血病B细胞对多药方案化合物的体外化学敏感性。在本研究中，40%的样本在体外对CEOP方案成分耐药。MTT在预测对CEOP方案的临床反应方面的可能作用仍需通过前瞻性的体外和体内研究来确定。
