利妥昔单抗治疗糖皮质激素无效的特发性血小板减少性紫癜疗效观察

Rituximab treatment for adults with steroid-resistant idiopathic thrombocytopenic purpura

目的探讨利妥昔单抗治疗特发性血小板减少性紫癜（ITP）的疗效、安全性及治疗前后B细胞、血小板膜糖蛋白（GP）特异性自身抗体的变化。方法利妥昔单抗（375mg／m^2，每周1次，连用4周）治疗12例糖皮质激素治疗无效的ITP患者，监测治疗前后的血常规、血清免疫球蛋白定量（IgG、IgM、IgA）、血小板GPⅡb／Ⅲa和（或）GPⅠb／Ⅸ特异性自身抗体、CD3^＋、CD4^＋、CD8^＋、CD19^＋、CD20^＋细胞数。结果4例完全有效，3例部分有效，2例微效，3例无效。随访中位时间5（0．5～12）个月，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^＋细胞数（4．1±2．2）×10^6／L与治疗前（295．0±86．4）×10^6／L比较明显下降（P〈0．01）。无严重不良反应。结论利妥昔单抗治疗糖皮质激素无效的ITP患者安全、有效。

Objective To investigate the efficacy and safety as well as the effects of rituximab on B-lymphocytes and anti-platelet glycoprotein-specific antibodies, in patients with steroid-resistant idiopathic thrombocytopenic purpura （ITP）. Methods Twelve steroid-resistant ITP patients, 16 to 54 years old, received intravenous rituximab at the dose of 375 mg/m^2 once - weekly for 4 weeks. Lab studies included CBC, serum concentrations of IgG, IgM and IgA. CD3^＋, CD4^＋, CD8^＋, CD19^＋, CD20^ cell numbers were assayed by flow cytometry and anti-platelet glycoprotein-specific antibodies （GP Ⅱ b/Ⅲa, GP Ⅰ b/Ⅸ ） were assayed by monoclonal antibody-specific immobilisation of platelet antigens prior to and following rituximab therapy. Results A complete response （ platelet counts ≥ 100 × 10^9/L） was observed in 4 cases, a partial response （ platelet counts between 50 and 100 × 10^9/L） in 3 cases, a minor response （ platelet counts between 30 and 50 × 10^9/L） in 2 cases, and non response （ platelet counts 〈 30 × 10^9/L） in 3 cases. Responses were sustained 0.5 to 12 months （median 5 months ）. After 4 weeks of rituximab therapy, anti-platelet glycoprotein-specific antibodies （GP Ⅱ b/Ⅲa, GP Ⅰ b/Ⅸ） disappeared except one NR patient and CD19^＋/ CD20^＋ cells were almost depleted in all patients （295.0 ± 86. 4） × 10^6/L vs （4. 1 ± 2.2） × 10^6/L（ P 〈 0. 01 ）. As expected, the T cell counts, and the serum concentrations of IgG, IgM and IgA were not changed after therapy. No severe side effects were observed. Conclusion Rituximab may be an effective and safe treatment for adults with steroid-resistant ITP.