沙利度胺联合环孢素A及泼尼松治疗中低危骨髓增生异常综合征疗效及对Th17和Th22细胞水平的影响

Curative effect of combination therapy with thalidomide,cyclosporine, and prednisone to patients with low-intermediate risk myelodysplastic syndrome and their influence to Th17 and Th22 cells

目的应用沙利度胺联合环孢素A及泼尼松(TCP方案)治疗中低危骨髓增生异常综合征(MDS),观察临床疗效,并探讨TCP方案对Th17、Th22细胞水平的影响。方法 2009年6月-2013年9月兰州大学第二医院血液科收治的62例中低危MDS患者分为2组,A组(35例)接受TCP方案,B组(27例)单用环孢素A,评估TCP方案治疗的有效性。应用流式细胞技术检测治疗前后Th17、Th22细胞表达水平的变化,酶联免疫吸附实验检测细胞因子IL-17、IL-22、IFN-γ、IL-10。结果 A组有效23例(65.71%),高于B组(44.44%),两组比较差异有统计学意义(P<0.05)。对A组的23例和B组的13例进行了Th17和Th22细胞表达水平观察,与健康对照组比较,治疗前两组Th17和Th22细胞比例均有不同程度升高,P<0.05。与治疗前比较,两组Th17细胞在治疗后均减低(P<0.05),A组Th22细胞在治疗后减低(P<0.05),B组Th22细胞在治疗后差异无统计学意义(P>0.05)。两组治疗前IL-17、IL-22水平与健康对照组比较差异无统计学意义(P>0.05),治疗后IL-17、IL-22水平也无明显变化(P>0.05)。两组IFN-γ水平均较治疗前降低(P<0.05);A组IL-10水平在治疗后升高(P<0.05)。两组患者均未出现3、4级血液学毒性。A组9例和B组4例患者出现肝功能异常,A组1例患者出现肾功能异常,所有肝、肾功能异常者经停药或对症治疗后均好转。结论 TCP方案是治疗MDS的有效组合方案,联合检测Th17和Th22将有助于指导免疫调节剂的使用。

tients with low-intermediate 1 risk myelodysplastic syndrome （MDS） to observe the curative effect and analyze immunologic response ofT helper （Th） 17 and Th22 cells. Methods 62 MDS patients with low and intermediate risk were enrolled into the present study from June 2009 to Sept. 2013 and divided into two groups, Group A （n=35, thalidomide, CsA and prednisone） and Group B （ n=27, CsA as single agent）. The primary endpoint was to evaluate the efficacy of TCP therapy and its influence to Thl 7 and Th22 cells tested by flow cytometry. IL-17, IL-22, IFN-γ and IL-10 were measured by ELISA. Results The effective rate （65.71%） in Group A was significantly higher than that in Group B （44.44 % ）, P 〈 0.05. Result with flow cytometry showed that the percentages of circulating Th17 and Th22 cells were higher in both Group A and B before therapy than those in healthy control （Thl7 cells 1.83 ± 0.30% and 1.85 ± 0.43% v 0.93 ± 0.22% respectively, Th22 cells 4.45 ± 0.87 and 4.35 ± 0.88% v 2.77 ± 0.94% respectively, P 〈 0.05）, Thl7 cells decreased aftertreatment in both Group A and B（Group A 1.32 ± 025% v 1.83 ± 0.30% and Group B 1.26 ± 0.28% v 1.85± 0.43%, P 〈 0.05） comparing with that before therapy, Th22 cells decreased obviously in Group A （3.05 ± 0.63% v 4.45 ± 0.87%, P 〈 0.05） but not in Group B （3.79 ± 0.68% v 4.35 ± 0.88%, P 〉 0.05）. The levels of IL-17 and IL-22 in Group A and B before therapy of were increased mildly comparing with those in healthy control （P 〉 0.05） and had no significant change after treatment （P 〉 0.05）. But the level of IFN-y after treatment prominently decreased compared with that beforetreatment in both Group A and B （P 〈 0.05）. While the level of IL- 10 were increased in Group A after treatment （P 〈 0.05） but slightly elevated in Group B （P 〉 0.05）. No patients in Group A and B show any grade 3/4 hematologic toxicity. Abnormal liver function was found 9 patients in Group A and 4 ones in Group B. 1 patient was found abnormal renal function in Group A. The patients with abnormal liver and renal function got recovery by stopping or symptomatic treatment. Conclusion TCP regimens were an effective formula for treatment of MDS. The detection of Th22 cells along with Th 17 cells could guild the use of immune modulator and worth further study.