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两种预处理方案用于自体外周血干细胞移植治疗重症系统性自身免疫性疾病的前瞻性随机研究

[A prospective and randomized study of two conditioning regimens in treatment of severe systemic autoimmune diseases with autologous peripheral blood stem cell transplantation].

作者信息

Zhang Wei, Zhou Dao-bin, Zhao Yan, Leng Xiao-mei, Zhang Jie-ping, Jiang Ying, Jiao Li, Wang Shu-jie, Duan Ming-hui, Tang Fu-lin, Shen Ti

机构信息

Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2007 Jun 26;87(24):1689-92.

PMID:17825150
Abstract

OBJECTIVE

To investigate the differences in immune reconstitution, hematopoietic reconstitution, efficacy, and complication between the two conditioning regimens with or without total body irradiation (TBI) in patients with refractory and severe autoimmune diseases (AID) who receiving autologous peripheral blood stem cell transplantation (APBSCT).

METHODS

Thirty-two AID patients, 5 males and 27 females, aged 29 (15 - 49), underwent APBSCT. The CD34(+) cells were mobilized with cytoxan (CTX) + granulocyte-colony stimulating factor (G-CSF) and selected by clinical magnetic activated cell sorting (CliniMACS). The conditioning regimen included CTX + antithymocyte globulin (ATG) in 11 patients and CTX + TBI in 21 patients. All the patients were followed up for more than 12 months.

RESULTS

The median time of granulocyte recovery were 11 and 9 days in the CTX + TBI and CTX + ATG groups respectively (P = 0.003), the median time of platelet recovery were 13 and 8 days respectively (P = 0.001). In both groups, the lymphocyte subsets were recovered with the inverted CD4/CD8 ratio 12 months after transplantation. Relapse was seen in 3 cases of the CTX + TBI group (14.3%), and 2 cases of the CTX + ATG group (18.2%), and the rest of patients remained free of AID. During transplantation incidence of bacteria infection occurred in 5 of the 21 cases in the CTX + TBI group (23.8%) and in 2 of the 11 cases of the CTX + ATG group (18.2%) respectively; viral infection occurred in 1 of the 21 cases of the CTX + TBI group (4.8%) and in 2 of the 11 cases of the CTX + ATG group (18.2%) respectively. The number of radiated parotitis was 4 among the 21 patients of the CTX + TBI group (19%) and was 3 among the 12 patients of the CTX + ATG group (25%). Serum sickness reaction occurred in 3 of the 12 patients of the CTX + ATG group (25%). Bacterial and viral infections were cured soon after antibacterial or antiviral therapy, no fatal bleeding occurred due to thrombocytopenia in both groups.

CONCLUSION

The conditioning regimen of TBI + CTX delays the hematopoietic reconstitution compared with the ATG + CTX regimen in treating AID. The regimen of CTX + TBI can be better tolerated, but there are no significant differences in efficacy and immune reconstitution among these two regimens.

摘要

目的

探讨在接受自体外周血干细胞移植(APBSCT)的难治性重症自身免疫性疾病(AID)患者中,含或不含全身照射(TBI)的两种预处理方案在免疫重建、造血重建、疗效及并发症方面的差异。

方法

32例AID患者,男5例,女27例,年龄29(15 - 49)岁,接受APBSCT。采用环磷酰胺(CTX)+粒细胞集落刺激因子(G-CSF)动员CD3⁴⁺细胞,并通过临床磁性激活细胞分选(CliniMACS)进行筛选。11例患者的预处理方案为CTX +抗胸腺细胞球蛋白(ATG),21例患者的预处理方案为CTX + TBI。所有患者均随访12个月以上。

结果

CTX + TBI组和CTX + ATG组粒细胞恢复的中位时间分别为11天和9天(P = 0.003),血小板恢复的中位时间分别为13天和8天(P = 0.001)。两组患者移植后12个月淋巴细胞亚群均恢复,CD4/CD8比值倒置。CTX + TBI组3例(14.3%)复发,CTX + ATG组2例(18.2%)复发,其余患者AID未复发。移植期间,CTX + TBI组21例中有5例(23.8%)发生细菌感染,CTX + ATG组11例中有2例(18.2%)发生细菌感染;CTX + TBI组21例中有1例(4.8%)发生病毒感染,CTX + ATG组11例中有2例(18.2%)发生病毒感染。CTX + TBI组21例患者中放射性腮腺炎4例(19%),CTX + ATG组12例患者中3例(25%)。CTX + ATG组12例患者中有3例(25%)发生血清病反应。细菌和病毒感染经抗菌或抗病毒治疗后很快治愈,两组均未因血小板减少发生致命性出血。

结论

在治疗AID方面,与ATG + CTX方案相比,TBI + CTX预处理方案延迟了造血重建。CTX + TBI方案耐受性较好,但两种方案在疗效和免疫重建方面无显著差异。

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