川芎嗪联合环孢霉素A 逆转恶性淋巴瘤多药耐药的研究*

目的：探讨川芎嗪、环孢霉素A 逆转恶性淋巴瘤（ML）多药耐药的机制和临床疗效。方法：120 例经病理组织学证实的复发、耐药的ML患者随机分入A 组（川芎嗪+ 环孢霉素A+化疗）、B 组（环孢霉素A+化疗）、C 组（川芎嗪+ 化疗）、D 组（化疗）。 流式细胞仪分析P-gp的表达，根据P-gp的表达情况进行亚组分析。结果：108 例患者有完整数据可供评估，A 组较D 组有无进展生存期（PFS）优势，差异有统计学意义（P=0.0346），而其他组之间的差异均无统计学意义（P 均>0.05）。 在ORR率方面，逆转剂组（A、B、C 组）较对照组（D 组）均有显著优势，差异有统计学意义（P 均<0.05）。 亚组分析：P-gp（+）76例，在PFS 方面，A、C 组较D 组有优势，差异有统计学意义（P 均<0.05）；B 组较D 组有一定的优势，但差异无统计学意义（P=0.0958）；A 组较B、C 组有一定的优势，但差异无统计学意义（P>0.05）。 在ORR率方面，逆转剂组（A、B、C 组）较对照组（D 组）均有显著优势，差异均有统计学意义（P 均<0.05）；A 组较B、C 组有优势，差异有统计学意义（P<0.05）。 P-gp（-）32例患者，在PFS ，ORR方面，各组间差异均无统计学意义（P均>0.05）。 川芎嗪、环孢霉素A 未增加明显的不良反应。结论：川芎嗪、环孢霉素A 可在一定程度上逆转ML的多药耐药，与P-gp的表达密切相关，两者联合用药疗效更佳。

Study on Reversal of Multidrug Resistance in Malignant Lymphoma by Combining Tetramethylpyrazine with Cyclosporine A

Objective:To explore the mechanism and reversing effect of tetramethylpyrazine (TMPZ) and cyclosporine A (CsA) on multidrug resistance (MDR) in treating malignant lymphoma (ML). Methods:A total of120 ML patients with pathologically confirmed relapse and drug resistance were randomly divided into four groups: (A) TMPZ + CsA + chemo-therapy, (B) CsA + chemotherapy, (C) TMPZ + chemotherapy and (D) chemotherapy alone. Flow cytometry was used to an -alyze the P-gp expression, and sub-group analysis was conducted based on the P-gp expression.Results: Complete data for 108 of the 120 patients were available for evaluation. The progression-free survival (PFS) of the patients was higher in group (A) than in group (D) (P=0.0346). There were no statistically significant differences in the comparison between the other two groups (P>0.05). There was a higher overall response rate (ORR) in the reversal-agent groups (A, B and C) than in the control group (D) (P<0.05). The subgroup analysis has shown that P-gp (+) was seen in 76patients. The PFS of the patients with P-gp (+) was higher in group (A) and (C) than in group (D), with statistical differences among the groups (P<0.05). The PFS of patients with P-gp (+) was higher in group (B) than in group (D), nevertheless, there were no statistical differences between the two groups (P>0.05). The ORR was higher in the patients with P-gp (+ ) in the reversal agent groups (A, B and C) than those in the control group (D), with statistical differences among the groups ( P<0.05). There was a manifest advantage in the ORR in group (A) compared with that in groups (B) and (C), (P<0.05). P-gp (-) was seen in 32 patients. Concerning PFS and ORR of the patients, there were no statistically significant differences in comparison among the groups ( P>0.05). No obvious adverse side effects were seen with TMPZ and CsA treatments. Conclusion:TMPZ and CsA can, to a certain degree, reverse MDR in relapsed or refractory ML and is closely correlated with the P-gp expression. There is an improved curative effect in the combined therapy of the two drugs.