利妥昔单克隆抗体和地塞米松联合环磷酰胺治疗复发难治的免疫性血小板减少症

Rituximab and Dexamethasone Combined with Cyclophosphamide for Treatment of Relapsed and Refractory Immune Thrombocytopenia

目的:评估利妥昔单克隆抗体和地塞米松联合环磷酰胺治疗复发难治的免疫性血小板减少症(ITP)的有效性、安全性及其可能的作用机制。方法:前瞻性纳入12例复发难治的ITP患者,给予利妥昔单克隆抗体375 mg/m^2,每周1次,连用4周;地塞米松40 mg,连用4d环磷酰胺500 mg/m^2,两周1次,连用2周。用ELISA法检测患者治疗前后外周血IFN-r和IL-4水平,流式细胞术检测治疗前后调节性淋巴细胞Breg、Treg和Th17的水平,同时观察治疗前后血小板计数的变化,监测不良反应。结果:12例患者中6例(50.00%)获得完全缓解,4例(33.33%)部分缓解,总有效率为83.33%。治疗前血小板计数的平均值为(12.83±6.01)×10~9/L,治疗后血小板的平均峰值为(115.42±76.60)×10~9/L,二者差异有显著统计学意义(P<0.001)。治疗后IFN-r/IL-4比值(5.89±2.30)较治疗前(7.00±2.73)下降,差异均有显著统计学意义(P=0.002)。治疗后外周血Breg细胞(21.27±4.28)%较治疗前(15.48±1.67)%升高(P<0.001),Treg/Th17比值(3.07±1.50)较治疗前(0.98±0.45)升高(P<0.001),差异均有显著统计学意义。不良反应为输液反应(1例),继发性高血压和高血糖(1例),呼吸道感染(2例)。结论:利妥昔单克隆抗体和地塞米松联合环磷酰胺可改善复发难治ITP患者的疗效,且患者耐受性较好,其机制可能为促使辅助T细胞亚群及调节性淋巴细胞达到平衡。

Objective:To evaluate the efficiency and safety of rituximab and dexamethasone combined with cyclophosphamide for treating patients with relapsed and refractory immune thrombocytopenia(ITP).Methods:Twelve patients with relapsed and refractory immune thrombocytopenia were prospectively enrolled in this study,and received rituximab 375 mg/m once a week for 4 weeks,dexamethasone 40 mg once a day for consecutive 4 days,and cyclophosphamide 500 mg/m biweekly for 2 weeks.The levels of IFN-r and IL-4 in peripheral blood of patients were measured by enzyme-linked immunosorbent assay(ELISA),and the percentages of Breg,Treg and Th17 cells were detected by flow cytometry before and after treatment.Efficiency was evaluated according to platelet counts,and side effects were observed.Results:Six out of 12 patients reached to complete remission and 4 patients reached to partial remission,with the total response rate 83.33%.The platelet counts[(115.42 ±76.60) × 10 /L]after treatment were significantly higher than that before treatment[(115.42 ±76.60)×l0~9/L](P<0.001).The ratio of IFN-r/ IL4 after treatment(5.89 ± 2.30) was very significantly lower than that before treatment(7.00 ± 2.73)(P = 0.002).The percentage of Breg cells after treatment[(21.27 ± 4.28)%]were much significantly higher than that before treatment[(15.48+1.67)%](P <0.001).The ratio of Treg/Th17 after treatment(3.07 ± 1.50) was significantly higher than that before treatment(0.98 ± 0.45)(P < 0.001).Infusion reaction was observed in 1 patient,secondary hypertension and hyperglycemia were in 1 patient,and pneumonia in 2 patients.Conclusion:Rituximab and dexamethasone combined with cyclophosphamide can improve the outcomes of patients with relapsed and refractoryimmune thrombocytopenia patients and they were well tolerated,its mechanism may be related with the balance between T cell sunsets and Treg cells.