标准剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症的临床研究  

Clinical study of standard dose of rituximab for the treatment of refractory primary immune thrombocytopenia

作　　者：朱愿超[1] 王文[1] 周郁鸿[2] 王晓敏[3] 王欣[4] 王毅丽 孙桂珍[6] 侯明[1] 

机构地区：[1]山东大学齐鲁医院,济南250012 [2]浙江省中医院 [3]新疆维吾尔自治区人民医院 [4]山东省立医院 [5]威海市立医院 [6]临沂市沂水中心医院

出　　处：《中华血液学杂志》2011年第3期163-167,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金（30600259、30600680、30770922、30570779）;国家“973”项目（2006cB50503803）;教育部全国优秀博士论文专项基金（200561）;新世纪优秀人才支持计划（NCET-07-0514）;教育部科学技术研究重点项目（109097）;卫生部临床学科重点项目（2007-2009）;国家卫生行业公益性科研专项基金（200802031）;教育部科技创新工程重大项目培育资金（704030）;泰山学者岗位基金;山东省中医药科技发展计划（2005-049）

摘　　要：目的探讨标准剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症（ITP）的疗效、安全性及治疗前后B细胞、血小板膜糖蛋白特异性自身抗体的变化。方法利妥昔单抗每周375mg／m^2，静脉滴注，连用4周，治疗31例复发难治性ITP患者，不伴随使用免疫抑制剂、化疗药、抗凝药及激素冲击疗法。监测治疗前后的血常规，血清免疫球蛋白（IgG、IgM、IgA），血小板GPⅡb／Ⅲa和（或）GPⅠb／Ⅸ特异性自身抗体及CD3^＋、CD4^＋、CD8^＋、CD19^＋、CD20^＋细胞数。结果12例完全有效，7例有效，12例无效。中位疗效持续时间6（2—48）个月，有效患者4例复发，其余疗效均维持较好。有效患者治疗后血小板自身抗体均转阴。治疗前后外周血血红蛋白、白细胞计数无明显变化，血清IgG、IgM、IgA无明显变化，CD3^＋、CD4^＋、CD8^＋细胞数无明显变化。治疗后CD19^＋／CD20^＋细胞明显下降。多数患者耐受好。结论利妥昔单抗治疗复发难治性ITP疗效肯定，不良反应可以耐受。Objective To evaluate the efficacy and safety of rituximab on B-lymphocytes and antiplatelet glycoprotein-specific antibodies in patients with refractory primary immune thrombocytopenic （ITP）. Methods Thirty-one ITP patients with a median age of 36 years （range 16 -56 years） received solely intravenous rituximab at the dose of 375 mg/m^2 once weekly for consecutive 4 weeks. Lab studies included complete blood count, serum concentrations of IgG, IgM and IgA. CD3^＋ , CD4^＋ , CD8^＋ , CD19^＋ and CD20^＋ cell numbers were assayed by flow cytometry and anti-platelet glycoprotein-specific antibodies （ GP Ⅱ b/Ⅲ a, GP Ⅰ b/Ⅸ） were assayed by monoclonal antibody-specific immobilisation of platelet antigens （MAIPA） prior to and following rituximab therapy. The response was evaluated according to the response criteria of international working group of ITP. Results Complete responses were achieved in 12 cases, response in 7 cases, and no response in 12 cases. Responses were sustained 2 to 28 months （median 6 months） with 4 cases relapsed. After 4 weeks of rituximab therapy, GP Ⅱ b/Ⅲ a, GP Ⅰ b/Ⅸ disappeared in responded patients, and CD 19^＋/CD20^＋ cells were almost depleted in all patients. As expected, the serum concentrations of IgG, IgM, IgA, and the T cell counts were not changed after therapy. Four patients developed infusion-related reaction, l impaired renal function, and 3 secondary infections. Conclusion Rituximab is effective and safe, and the adverse reaction is tolerable.

关 键 词：紫癜 血小板减少性 特发性 难治性 抗体 单克隆 CD20 

分 类 号：R558.2[医药卫生—血液循环系统疾病]