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单倍型人类白细胞抗原配型造血干细胞移植治疗恶性血液病的临床研究

[Clinical study on haploid HLA-matched hematopoietic stem cell transplantation for treatment of malignant hematological disease].

作者信息

Sun Ai-Ning, Wu De-Pei, Wang Ying, Qiu Hui-Ying, Jin Zheng-Ming, Miao Miao, Tang Xiao-Wen, Fu Zheng-Zheng, Ma Xiao, Han Yue, He Guang-Sheng, Chen Su-Ning, Xue Sheng-Li, Zhao Ye

机构信息

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Jiangsu, Suzhou 215006, P. R. China.

出版信息

Ai Zheng. 2006 Aug;25(8):1019-22.

Abstract

BACKGROUND & OBJECTIVE: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective method to treat malignant hematological disease. However the human leukocyte antigen (HLA)-matched sibling donors can be found for only 25%-30% patients. The probability of finding an unrelated matched donor is 1/50000-1/100000, or even lower. If we choose haploid HLA-matched hematopoietic stem cell transplantation instead, we may be able to find donors for 90% patients. Our present study was to explore the feasibility of allo-HSCT by using haploid HLA-matched donor in treatment for malignant hematological disease.

METHODS

Twenty-five patients with malignant hematological disease received allo-HSCT with HLA 2 or 3 antigen mismatched related donors. All patients were treated with intensive immunosuppression, granulocyte colony stimulating factor (G-CSF) mobilization, antithymocyte globulin (ATG) and combination of bone marrow and peripheral blood stem cell transplantation. The conditioning regimen was intensified and prolonged by using the combination of cyclosporine (Cs) A, MMF, ATG and anti-CD25 antibody for graft-versus-host disease (GVHD) prophylaxis.

RESULTS

All patients achieved sustained, full donortype engraftment. Acute GVHD occurred in 21 of 25 patients. Eight of them were grade I aGVHD, six grade II aGVHD, two grade III aGVHD and five grade IV aGVHD. The cumulative incidence of grade II-IV aGVHD was 48%,and grade III-IV aGVHD was 28.57%. Chronic GVHD was observed in 12 of 25 patients and none of them developed extensive cGVHD. Sixteen patients were alive and disease free, with 64.0+/- 2.98% 1 year disease-free survival rate. One year overall survival rate was 64.0+/-3.08%. Nine patients died, 1 from relapse and 8 from transplantation related mortality.

CONCLUSIONS

Haploid HLA-matched allo-HSCT is a relatively efficient method for the treatment of patients with malignant hematological disease, who have no related matched donors. Nevertheless, strict administration should be carried out since it's a high risk approach.

摘要

背景与目的

异基因造血干细胞移植(allo-HSCT)是治疗恶性血液病最有效的方法。然而,仅25%-30%的患者能找到人类白细胞抗原(HLA)匹配的同胞供者。找到无关匹配供者的概率为1/50000-1/100000,甚至更低。若选择单倍体HLA匹配的造血干细胞移植,90%的患者或许能找到供者。本研究旨在探讨采用单倍体HLA匹配供者进行allo-HSCT治疗恶性血液病的可行性。

方法

25例恶性血液病患者接受了HLA 2或3个抗原不相合的相关供者的allo-HSCT。所有患者均接受强化免疫抑制、粒细胞集落刺激因子(G-CSF)动员、抗胸腺细胞球蛋白(ATG)以及骨髓和外周血干细胞移植联合治疗。通过使用环孢素(Cs)A、霉酚酸酯(MMF)、ATG和抗CD25抗体联合方案预防移植物抗宿主病(GVHD),强化并延长预处理方案。

结果

所有患者均实现了持续、完全的供者型植入。25例患者中有21例发生了急性GVHD。其中8例为Ⅰ级急性GVHD,6例为Ⅱ级,2例为Ⅲ级,5例为Ⅳ级。Ⅱ-Ⅳ级急性GVHD的累积发生率为48%,Ⅲ-Ⅳ级为28.57%。25例患者中有12例观察到慢性GVHD,且均未发生广泛型慢性GVHD。16例患者存活且无病,1年无病生存率为64.0±2.98%。1年总生存率为64.0±3.08%。9例患者死亡,1例死于复发,8例死于移植相关死亡率。

结论

单倍体HLA匹配的allo-HSCT是治疗无相关匹配供者的恶性血液病患者的一种相对有效的方法。然而,由于其风险较高,应严格管理。

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