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[两种HLA配型不合的异基因造血干细胞移植治疗血液系统恶性肿瘤]

[Two Kinds of HLA-mismatched Allogeneic Hematopoictic Stem Cell Transplantation for Treatment of Hematologic Malignancies].

作者信息

Li Wei-Da, Gao Zhi-Yong, Yu Xin-Jian, Lu Da-Yu, Lu Dao-Pei

机构信息

Center of Hematopoietic Cell Transplantation, Shanghai Dao-Pei Hospital, Fudan University; The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.

Center of Hematopoietic Cell Transplantation, Shanghai Dao-Pei Hospital, Fudan University; The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China. E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Apr;24(2):562-7. doi: 10.7534/j.issn.1009-2137.2016.02.048.

Abstract

OBJECTIVE

To investigate the safety and effectiveness of HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with related haploidentical bone marrow infusion for treatment of hematologic malignancies and to explore the mathod for reduction of aGVHD incidence and clinical significance.

METHODS

A total of 30 patients with hematologic malignancies (8 cases of AML, 17 AML, 2 MDS and 3 Mix-AL) received related haploidentical and unrelated HLA-mismatched allo-HSCT combined with related haploidentical bone marrow infusion. Among them 20 cases received related haploidentical transplantation of the first donor, 10 cases received unrelated HLA-mismatched treaplantation. The new conditioning regimen for the patients underwent allo-HSCT consisted of fludarabine, busulfan, Me-CCNU and cyclophosphamide. The drugs for GVHD prophylaxis included cyclosporine A and methotrexate, while mycophenolate mofetil and rabbit anti-T-lymphocyte globulin (ATG) were used.

RESULTS

All the patients achieved full engraftment. The median time for neutrophils to reach over 0.5 × 10(9)/L was 14 days (8-26 days), while the median time for platelets to reach over 20 × 10(9)/L was 11.5days (10-24 days). The incidence of I-II grade of aGVHD at 100 d was 22.28% (95% CI 9.9%-34.7%), the incidences of II-IV and III-IV grade of aGVHD were 22.7% (95% CI, 10%-35.4%) and 12.7% (95% CI 6.9%-15.5%) respectively. The incidences of I-II and III-IV cGVHD were 13.3% (95% CI, 1.4%- 26.8%) and 3.3 % (95% CI, 0%-12.2%), one case (3.3%) was in extensive cGVHD. DFS and OS of 2 years were 81.1% (95% CI, 66.0%-96.2%) and 68.2% (95% CI 51.0%-85.4%).

CONCLUSION

These data suggest that the incidence of grade II-IV grade of aGVHD in recipients of 2 partially HLA-matched units was lower, co-infusion of haplo-BM and partially matched units in allogeneic transplantation is safe and effective for reducing the incidence of aGVHD and improving the survival in DFS.

摘要

目的

探讨人类白细胞抗原(HLA)配型不合的异基因造血干细胞移植(allo-HSCT)联合相关单倍体相合骨髓输注治疗血液系统恶性肿瘤的安全性和有效性,并探索降低急性移植物抗宿主病(aGVHD)发生率的方法及其临床意义。

方法

30例血液系统恶性肿瘤患者(急性髓系白血病8例、急性淋巴细胞白血病17例、骨髓增生异常综合征2例、混合细胞白血病3例)接受了相关单倍体相合及HLA配型不合的allo-HSCT联合相关单倍体相合骨髓输注。其中20例接受第1供者的相关单倍体相合移植,10例接受HLA配型不合的非血缘移植。allo-HSCT患者的新预处理方案包括氟达拉滨、白消安、司莫司汀和环磷酰胺。预防移植物抗宿主病的药物包括环孢素A和甲氨蝶呤,同时使用霉酚酸酯和兔抗人T淋巴细胞球蛋白(ATG)。

结果

所有患者均实现完全植入。中性粒细胞计数达到0.5×10⁹/L以上的中位时间为14天(8 - 26天),血小板计数达到20×10⁹/L以上的中位时间为11.5天(10 - 24天)。100天时I-II级aGVHD的发生率为22.28%(95%可信区间9.9% - 34.7%),II-IV级和III-IV级aGVHD的发生率分别为22.7%(95%可信区间10% - 35.4%)和12.7%(95%可信区间6.9% - 15.5%)。I-II级和III-IV级慢性移植物抗宿主病(cGVHD)的发生率分别为13.3%(95%可信区间1.4% - 26.8%)和3.3%(95%可信区间0% - 12.2%),1例(3.3%)为广泛型cGVHD。2年无病生存率(DFS)和总生存率(OS)分别为81.1%(95%可信区间66.0% - 96.2%)和68.2%(95%可信区间51.0% - 85.4%)。

结论

这些数据表明,接受2个部分HLA匹配单位移植的受者中II-IV级aGVHD的发生率较低,异基因移植中联合输注单倍体骨髓和部分匹配单位对于降低aGVHD发生率及提高DFS生存率是安全有效的。

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