小剂量利妥昔单抗治疗难治及复发性温抗体型AIHA临床研究

Clinical research of low-dose rituximab therapy for patients with refractory and relapsed autoimmune hemolytic anemia

目的探讨小剂量利妥昔单抗治疗难治及复发温抗体型自身免疫性溶血性贫血(AIHA)的有效性和安全性。方法研究纳入11例难治及复发温抗体型自身免疫性溶血性贫血患者,给予利妥昔单抗100 mg静脉滴注,每周1次,连用4周;通过动态观察血红蛋白、网织红细胞、总胆红素、间接胆红素、乳酸脱氢酶及直接抗人球蛋白试验(DAT)变化评价疗效,采用流式细胞术检测治疗前后CD3^+、CDl9^+CD20^+淋巴细胞数,免疫比浊法定量检测治疗前后血清免疫球蛋白(IgG、IgM、IgA)水平。结果治疗后,11例患者中5例(45.45%)完全缓解,3例(27.27%)部分缓解,而3例(27.28%)无效,总有效率为72.72%。小剂量利妥昔单抗治疗前后血清免疫球蛋白及CD3^+淋巴细胞数无明显变化(P>0.05),但CDl9^+CD20^+淋巴细胞数较治疗前明显下降(P<0.01),并达到清除水平。2例患者输注小剂量利妥昔单抗过程中发生输液反应,1例随访期间发生细菌性肺炎,经抗感染后治愈。结论小剂量利妥昔单抗治疗难治及复发温抗体型自身免疫性溶血性贫血安全、有效的,但其最佳用药方案尚需更多临床患者观察加以验证。

Objective To investigate the efficacy and safety of 1ow-dose rituximab therapy for patients with refractory and re1apsed au-toimmune hemo1ytic anemia（AIHA）. Methods E1even patients with refractory and re1apsed AIHA received intravenous rituximab at the dose of 100 mg once week1y for 4 consecutive weeks. The efficacy of 1ow-dose rituximab therapy was eva1uated through dynamic changes of heamog1obin,reticu1ocyte,tota1 bi1irubin,indirect bi1irubin,1actate dehydrogenase and direct antig1obu1in test（DAT）. The serum concentrations of immunog1obu1in（ IgG,IgM and IgA）were quantitated by immunoturbidimetry. The numbers of CD3 ＋ and CD19 ＋ CD20 ＋ 1ymphocyte ce11s were assayed by f1ow cytometry prior to and fo11owing therapy. Results The responses were 5 （45. 45% ）CR,3（27. 27% ）PR,and 3（27. 28% ）NR,respective1y. As a resu1t,the tota1 effective rate was 72. 72% . There were no significant changes of serum immunog1obu1in and CD3 ＋ 1ymphocyte counts during prior and post treatment（P 〉 O. 05）. However, CD19 ＋ CD20 ＋ ce11s were a1most decreased to dep1etion 1eve1 in the patients treated with 1ow-dose rituximab. Infusion reaction was ob-served in two patients. One patient suffered from bacteria1 pneumonia which was cured by anti-infection. Conclusion Treatment with 1ow dose rituximab may be an effective and safe approach for patient with efractory and re1apsed AIHA. However,the optima1 therapeu-tic schedu1e needs further investigation.