CD34^+细胞自身移植治疗儿童难治性系统性红斑狼疮

Application of CD34^+ autologous peripheral progenitor cell transplant in the treatment of children with refractory SLE

目的 探讨CD34+ 细胞分选的自身干细胞移植在儿童难治性系统性红斑狼疮 (SLE)中的治疗效果。方法 2例病程分别为 5年和 7年、狼疮肾 III级和IV级、主要表现为持续性血小板减少、蛋白尿和胸腔积液的患儿 ,首先经重组人粒细胞集落刺激因子动员、CS 30 0 0血细胞分离机采集外周血 ,获取单个核细胞 ,通过CliniMACSCD34+ 细胞分选仪分别得到了 1 7× 1 0 6 /kg及 1 0× 1 0 6 /kgCD34+ 细胞 ,采集物中分别尚存 2× 1 0 5/kg及 1× 1 0 4 /kg的CD3+ 细胞。然后给予患儿环磷酰胺[50mg/ (kg·d)× 4d]和抗胸腺细胞球蛋白 [5mg/ (kg·d)× 3d]预处理 ,48h后回输冻存的CD34+ 细胞。结果 两患儿分别于移植后 9和 7天即获粒细胞重建 ,自 1 5天起血小板一直维持在正常水平。因停用皮质激素 ,移植 3个月后患儿库欣征完全消退 ,1例患儿还获得了自患病 7年来的首次身高增长 (半年内身高增长了 5cm)。现已分别随访 1 3个月和 6个月 ,原发病症状完全消失、自身免疫相关抗体全部转阴 ,但细胞免疫功能仍未恢复 ,CD4仍处于低水平。结论 CD34+

Objective Systematic lupus erythematosis (SLE)is a severe disease which affects the patient for many years and there is no radical cure for the disease To explore a possible way to treat children with refractory SLE, the authors treated 2 children with grade III and IV lupus nephropathy for 5 years and 7 years respectively, mainly presented with persistent thrombocytopenia, proteinuria, pleural effusion with CD34 + autologous peripheral progenitor cells transplantation Methods Mobilized with G CSF and collected with CS 3000 Cell Separator, passed through the CliniMacs CD34 + cell selection device, the count of CD34 + cells obtained reached 1 0 ×10 6/kg and 1 7× 10 6/kg, respectively with the remaining of 2 0×10 5/kg and 1 0×10 4/kg of CD3 + cells individually The selected CD34 + cells were frozen at -80℃. The conditioning regimen consisted of cyclophosphamide [50 mg/(kg·day) for 4 days] plus ATG [Fresennius S 5 mg/(kg·day) for 3 days] After 48 h treatment with cyclophosphamide, the frozen stem cells were infused back to the patients Results Neutrophils recovered on 9 and 7 days after transplantation respectively in these 2 cases Beginning from 15 days, the platelet count recovered and remained at over 100×10 9/L. The sign of Cushing′s syndrome disappeared completely 3 months after transplantation because discontinuing the steroid One child′s height had a 5 cm increase within 6 months after stopping steroid and this was the first height gain during the 7 years since she had had the disease Till this paper was written, these 2 children were followed up for 13 months and 6 months, respectively, all the original symptoms and autoantibodies related to autoimmune disorders disappeared But the cell mediated immunity did not recover yet with the CD4 + cell level still remained at a lower level Conclusion The effect of CD34 + autologous peripheral progenitor cell transplantation on the children with refractory SLE was satisfactory so far, but the long term effect remains to be confirmed by further studies on more cases