Zhao Yan, Zhou Dao-bin, Leng Xiao-mei, Wang Shu-jie, Li Tai-sheng, Duan Yun, Shen Ti, Zhao Yong-qiang, Zhang Jie-ping, Bai Lian-jun, Cui Wei, Zhang Fu-quan, Zeng Xiao-feng, Zhang Feng-chun, Dong Yi, Tang Fu-lin
Department of Rheumatology, Peking Union Medical College Hospital, Beijing 100730, China.
Zhonghua Yi Xue Za Zhi. 2004 Dec 17;84(24):2077-81.
To investigate the feasibility, efficacy and safety of high dose immunosuppressive therapy (HDIT) and autologous peripheral blood stem cell transplantation (PBSCT) with CD(34)(+) cell selection in patients with refractory and severe autoimmune diseases.
Twenty-one patients with SLE, RA, pSS, SSc or MCTD were enrolled in the study from 1999. Autologous haemopoietic stem cells were mobilized with CTX 3 approximately 4 g/m(2) and granulocyte colony stimulating factor (G-CSF). CD(34)(+) cells were selected by CliniMACS. After conditioning with CTX (200 mg/kg) and pig antithymocyte globulin (ATG, 90 mg/kg) or CTX (150 mg/kg) and total body irradiation (TBI, 4 approximately 6 Gy), the enriched CD(34)(+) cells were reinfused.
All patients completed the mobilization and leukapheresis procedures successfully, and proceeded to receive conditioning and transplantation. Two patients died of complication related to transplantation, one is CMV infection, the other is severe pneumonia during the course of granulocyte deficiency. A MCTD patient completed the stem cell mobilization and died of severe pulmonary hypertension and heart failure before CD(34)(+) cells reinfusing. Two SLE patients relapsed in 26, 37 months respectively and a RA patient relapsed in 15 months after transplantation. Other patients got improved, with SLE-DAI score decreasing from 17 to 4 score and proteinuria decreasing from 6.7 g to 2.3 g in SLE patients; DAS28 score from 7.9 to 2.1 in RA patient; Symptom improved and lab results recovered in SS.
High dose immunosuppressive therapy followed by autologous peripheral blood stem cell transplantation with CD(34)(+) cell selection is feasible and relative safe. Patients remain free from disease active and improved continuously. Some patients could relapse after transplantation. Long-term effect need to be further observed.
探讨大剂量免疫抑制治疗（HDIT）联合经CD(34)(+)细胞分选的自体外周血干细胞移植（PBSCT）治疗难治性重症自身免疫性疾病患者的可行性、疗效及安全性。
自1999年起，21例系统性红斑狼疮（SLE）、类风湿关节炎（RA）、原发性干燥综合征（pSS）、系统性硬化症（SSc）或混合性结缔组织病（MCTD）患者纳入本研究。采用环磷酰胺（CTX）3约4 g/m(2)联合粒细胞集落刺激因子（G-CSF）动员自体外周血造血干细胞。通过CliniMACS分选CD(34)(+)细胞。经CTX（200 mg/kg）和猪抗胸腺细胞球蛋白（ATG，90 mg/kg）或CTX（150 mg/kg）联合全身照射（TBI，4约6 Gy）预处理后，回输富集的CD(34)(+)细胞。
所有患者均成功完成动员及白细胞单采程序，并接受预处理及移植。2例患者死于移植相关并发症，1例为巨细胞病毒（CMV）感染，另1例为粒细胞缺乏期的重症肺炎。1例MCTD患者完成干细胞动员，在回输CD(34)(+)细胞前死于重度肺动脉高压及心力衰竭。2例SLE患者分别于移植后26、37个月复发，1例RA患者于移植后15个月复发。其他患者病情改善，SLE患者的SLE-DAI评分从17分降至4分，蛋白尿从6.7 g降至2.3 g；RA患者的DAS28评分从7.9降至2.1；pSS患者症状改善，实验室检查结果恢复正常。
大剂量免疫抑制治疗后经CD(34)(+)细胞分选的自体外周血干细胞移植是可行且相对安全的。患者病情缓解且持续改善。部分患者移植后可能复发。长期疗效有待进一步观察。
