利妥昔单克隆抗体治疗不同激素敏感性的ITP患者的疗效比较

Curative Efficacy of Rituximab for ITP Patients with Different Sensitivity to Hormone

目的:观察小剂量利妥昔单克隆抗体治疗糖皮质激素无效和依赖的ITP患者的疗效及其与激素敏感性的关系,为临床医师合理用药提供参考。方法:将79例ITP患者纳入研究,其中对糖皮质激素无效的19例,对糖皮质激素依赖的有60例。对所有患者给予地塞米松40 mg/d×4,d 7、14、21、28静脉滴注利妥昔单克隆抗体100 mg,治疗后对所有患者随访12个月,分析患者对激素的敏感性与利妥昔单克隆抗体治疗反应的关系。应用流式细胞术及ELISA法检测治疗前后Tregs比例,BAFF、IL-2和sCD40L水平的变化。结果:79例ITP患者经地塞米松联合利妥昔单克隆抗体治疗后1、3、6及12个月的总有效率分别为79.7%(63/79)、69.6%(55/79)、63.3%(50/79)和60.8%(48/79),其中对糖皮质激素无效(n=19)和存在糖皮质激素依赖(n=60)的ITP患者1、3、6和12个目的总有效率分别为47.4%(n=9)vs 90.0%(n=54);36.8%(n=7)vs 80.0%(n=48);21.1%(n=4)vs 76.7%(n=46);21.1%(n=4)vs 73.3%(n=44),2组间差异具有统计学意义。进一步分析两组治疗后1、3、6及12个月2组Treg细胞比例分别为(1.70±0.43)%vs(3.47±0.72)%;(1.66±0.33)%vs(4.29±0.91)%;(1.71±0.37)%vs(4.44±0.97)%;(3.36±0.54)%vs(4.29±1.04)%。研究结果表明,糖皮质激素依赖患者在治疗1个月后血浆中BAFF,IL-2和sCD40L的水平明显降低(P<0.05),糖皮质激素无效患者的BAFF、IL-2和sCD40L水平虽然也有降低,但2组间差异无统计学意义。结论:对糖皮质激素依赖的患者应用利妥昔单克隆抗体治疗更有效,对Treg细胞、BAFF,IL-2和sCD40L调节是其可能机制之一。

Objective:To investigatc the curative efficacy of low dose rituximab for glucocorticoid ineffective on dependent ITP patients and its relation with sensitivity to glucocorticoid so as to provide reference basis for rational use of drugs in clinical treatmant.Methods:Seventy-ninth ITP patients enrolled in this study included the glucocorticoidineffective patients(19 cases)and glucocorticoid-dependent patients(60 cases).All ITP patients were treated with regimen consisted of high dose dexamethasone plus low dose rituximab(dexal-methasone 40 mg/d for 4 days per os,ritaximab 100 mg by intravenous infusion at D7,14,21 and 28 respectively).The patients after treatment were followedup for 12 month,and the relation of patients sensitivity to glucocorticoid with therapentic response of rituximab was analyzed.The changes of Treg cell ratio and BAFF,IL-2 and sCD40 L levels before and after treatment were detected by flow cytometry and ELISA respectively.Results:The overall response rate(ORR)of patients treated with abovementioned regemen at 1,3,6 and 12 months after treatment was 79.7%(63/79),69.6%(55/79),63.3%(50/79)and 60.8%(48/79)respectivcly,out of which the ORR of glucocorticoid ineffective and glucocorticoid-dependent ITP patients treated with above-mentioned regimen at 1,3,6 and 12 months after treatment was 47.4%(9/19)vs 90.0%(54/60),36.8%(7/19)vs 80.0%(48/60),21.1%(4/19)vs 76.7%(46/60),21.1%(4/19)vs 73.3%(44/60),and the difference between 2 groups was statistically significant.The detection of T reg cell showed that the T reg cell ratio in glucocorticoidineffective and dependent patients at 1,3,6 and 12 months after treatment was(1.70±0.43)%vs(3.47±0.72)%,(1.66±0.33)%vs(4.29±0.91)%,(1.71±0.37)%vs(4.44±0.97)%,(3.36±0.54)%vs(4.29±1.04)%,respectively.The detection of cytokines showed that the levels of BAFF,IL-2 and sCD40 L in plasma of glucocorticoid-dependent patients at 1 month after treatment significanlly decreased(P<0.05),the levels of BAFF,IL-2 and sCD40 L in plasma of glucocorticoid-ineffective patients although decreased at 1 mouth after treatment,but there was no statistical difference as compared with glucocosticoid-depenment patients.Conclusion:The treatment of glucocorticoid-dependent ITP patients with rituximab is more effective.The regulatory effect of rituximab on the T-reg cells,BAFF,IL-2 and sCD40 L may be one of its mechanisms.