小剂量利妥昔单抗治疗继发于CTD的TP序贯维持的疗效分析

Analysis on effect of low-dose rituximab sequential maintenance for treating thrombocytopenia secondary to connective tissue disease

目的探讨小剂量利妥昔单抗治疗继发于结缔组织疾病(CTD)血小板减少症(TP)序贯维持的临床疗效及安全性。方法选择16例继发于CTD的重症TP患者,给予利妥昔单抗100mg静脉滴注,每周1次,连用4周;动态观察血常规变化,采用流式细胞术检测治疗前、后CD3+、CD19+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、lgM、IgA)水平。治疗有效患者序贯给予每6个月静脉滴注利妥昔单抗100mg行维持治疗,通过长期随访评价维持治疗有效性。结果治疗后7例(43.75%)达完全缓解(CR),4例(25.00%)达有效(R),总有效率为68.75%,5例(31.25%)无效(NR)。患者利妥昔单抗治疗前、后血清免疫球蛋白及CD3+淋巴细胞数比较差异无统计学意义(P>0.05),但CD19+CD20+淋巴细胞数较治疗前明显下降(P<0.01),并达到清除水平。11例治疗有效患者接受了维持治疗,CR的7例患者均未复发,4例R患者中有2例在维持治疗期间获得CR,1例维持R,1例复发。4例发生轻度输液反应,1例发生肺炎,抗感染治疗后治愈。结论小剂量利妥昔单抗治疗继发于CTD的TP安全有效,而对治疗有效的患者序贯维持治疗能有效减少复发。

Objective To investigate the efficacy and safety of low-dose rituximab therapy and sequential maintenance for treating thrombocytopenia（TP）secondary to connective tissue disease（CTD）.Methods 16 patients with severe TP secondary to CTD were selected and given the intravenous drip of rituximab 100 mg,once weekly for 4consecutive weeks.The changes of blood routine were dynamically observed.The serum concentrations of immunoglobulin（IgG,IgM and IgA）were quantitatively detected by using the immunoturbidimetric method.The counts of CD3＋and CD19＋CD20＋lymphocyte cells were assayed by the flow cytometry before and after therapy.The patients acquiring effect were sequentially given the 6-month intravenous drip of rituximab100 mg for conducting the sequential maintenance therapy.The effectiveness of maintenance therapy was evaluated through longterm follow-up.Results After treatment,7cases（43.75%）reached the complete remission（CR）,4cases（25.00%）reached the response（R）,the total effective rate was 68.75%,but 5cases（31.25%）were non-response（NR）.The serum immunoglobulin and CD3＋lymphocyte counts had no significant changes between before and after treatment（P〉0.05）.However,the CD19＋CD20＋cells counts were decreased compared with before treatment（P〈0.01）,moreover which reached the clearing level.11 cases acquiring effect received the maintenance therapy,7cases of CR had no recurrence.Among 4cases acquiring R,2cases achieved CR during the maintenance therapeutic period,1case maintained R and 1case relapsed.4cases developed the mild infusion reaction,1case happened pneumonia and cured after anti-infection therapy.Conclusion The low dose rituximab is effective and safe in treating TP secondary to CTD,the sequential maintenance therapy in the patients acquiring effect could effectively reduce recurrence.