Peripheral blood CD34+ cell mobilization in 42 patients with severe autoimmune disease.

Wei Zhang, Dao-Bin Zhou, Yan Zhao, Jun-Ling Zhuang, Xiao-Mei Leng, Shu-Jie Wang, Li Jiao, Fu-Lin Tang, Jie-Ping Zhang, Xuan Wang, Ti Shen
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Abstract

Objective: To evaluate the feasibility and safety of peripheral CD34+ cell mobilization in patients with severe autoimmune disease.

Methods: Forty-two patients underwent a total of 46 mobilizations by the regimen of cyclophosphamide 2-3 g/m2+ recombinant human granulocyte colony stimulating factor (rhG-CSF) 5 microg x kg(-1) x d(-1). The positive selection of CD34+ cell was performed through the CliniMACS.

Results: In 8.1 +/- 2. 3 days after administration of cyclophosphamide, the peripheral white blood cell and mononuclear cell (MNC) decreased to the lowest level. In 3.7 +/- 1.6 days after injection of rhG-CSF, the peripheral absolute MNC and CD34+ cell counts were 0.95 x 10(9)/L and 0.035 x 10(9)/L, respectively. After 2.4 +/- 0.6 times of leukapheresis, there gained 4.46 x 10(8)/kg of MNC and 5.26 x 10(6)/kg of CD34+, respectively. After mobilization, the underlying diseases were ameliorated more or less. In systemic lupus erythematosus (SLE) patients, SLE Disease Activity Index (SLEDAI) decreased from a median of 17 to 3 (P < 0.01). In rheumatic arthritis patients, an American College of Rheumatology criteria for 20% (ACR20) response was achieved in all five patients. Totally, 17.4% of patients whose absolute neutrophil count < 0.5 x 10(9)/L suffered infection, and 31.0% of patients had bone pain after the injection of rhG-CSF. Two patients suffered severe complications, one with acute renal failure and recovered by hemodialysis, the other died of thrombotic thrombocytopenic purpura. Failed mobilization occurred in three patients.

Conclusions: Sufficient CD34+ cells can be mobilized by low dose of cyclophosphamide and rhG-CSF. CD34+ cell mobilization for treatment of severe autoimmune disease not only is appropriate in both effectiveness and safety but ameliorates disease also.

42例严重自身免疫性疾病患者外周血CD34+细胞动员的研究
目的:评价外周血CD34+细胞动员治疗严重自身免疫性疾病的可行性和安全性。方法:42例患者采用环磷酰胺2-3 g/m2+重组人粒细胞集落刺激因子(rhG-CSF) 5 μ g × kg(-1) × d(-1)方案,共进行46次动员。通过CliniMACS进行CD34+细胞的阳性选择。结果:8.1±2。环磷酰胺给药3 d后,外周血白细胞和单核细胞(MNC)降至最低水平。注射rhG-CSF后3.7 +/- 1.6 d,外周血绝对MNC和CD34+细胞计数分别为0.95 × 10(9)/L和0.035 × 10(9)/L。经2.4 +/- 0.6次白细胞分离后,MNC和CD34+分别增加4.46 × 10(8)/kg和5.26 × 10(6)/kg。活动后,基础疾病或多或少得到改善。在系统性红斑狼疮(SLE)患者中,SLE疾病活动指数(SLEDAI)从中位数17降至3 (P < 0.01)。在风湿性关节炎患者中,所有5例患者均达到了美国风湿病学会20% (ACR20)缓解标准。注射rhG-CSF后,17.4%的绝对中性粒细胞计数< 0.5 × 10(9)/L的患者发生感染,31.0%的患者发生骨痛。2例患者出现严重并发症,1例急性肾功能衰竭经血液透析恢复,另1例死于血栓性血小板减少性紫癜。3例患者活动失败。结论:低剂量环磷酰胺和rhG-CSF可动员足够的CD34+细胞。CD34+细胞动员治疗严重自身免疫性疾病不仅在有效性和安全性上都是合适的,而且还能改善疾病。
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