减低剂量预处理方案在亲缘HLA单倍体相合造血干细胞移植中的应用

Reduced-intensity conditioning regimen in HLA-haploidentical hematopoietic stem cell transplantation

背景:近年来减低剂量预处理异基因造血干细胞移植已被证明是安全有效的治疗手段,在同胞全相合和无关供者中应用逐年增多,它特别适合老年人或年轻人合并器官功能障碍的患者,然而由于找到HLA配型相合供体的概率不高,使得同胞全相合和无关供者减低剂量预处理异基因造血干细胞移植开展受限,而HLA不相合/单倍体供体则可以迅速找到,但减低剂量预处理的单倍体造血干细胞移植应用的报道还较少,国内尚未见报道,因此对减低剂量预处理的单倍体造血干细胞移植的开展情况进行综述非常重要。目的:综述减低剂量预处理在亲缘HLA单倍体造血干细胞移植中的应用现状。方法:以"减低剂量预处理方案、非清髓性预处理方案、HLA单倍体相合、造血干细胞移植和No-nmyeloablative conditioning,Reduced-intensity conditioning,HLA-haploidentical,Hematopoietic stem cell transplantation"为检索词,应用计算机检索1997至2014年万方数据库、CNKI和PubM ed数据库、外文医学信息资源检索平台检索关于减低剂量预处理在亲缘HLA单倍体造血干细胞移植中应用的相关文献,根据纳入标准和排除标准,最终选取25篇文献进行分析,全部为英文。结果与结论:减低剂量预处理异基因造血干细胞移植在HLA同胞全相合及无关供者中开展的较多且效果愈来愈好。减低剂量预处理的单倍体造血干细胞移植开展的较晚且报道较少,其植入、感染、移植相关死亡、移植物抗宿主病、长期无病生存率和总生存率等各个研究的结果差异较大,早期结果稍差,而近期总体情况有明显改善。目前看减低剂量预处理的单倍体造血干细胞移植是可行的,尤其对于找不到同胞相合及无关全相合供者的患者来说,HLA单倍体相合的血缘关系亲属成为最有潜力的干细胞来源。减低剂量预处理的单倍体造血干细胞移植保留较强的移植物抗白血病效应,且寻找供者容易,有足够的细胞后续治疗如供者淋巴细胞输注,同时通过发挥移植物抗白血病效应,可有效清除患者体内的肿瘤细胞,为处在疾病进展期或经历多次治疗失败的患者,尤其是老年患者、合并器官功能障碍及并发症患者,提供有效的挽救治疗手段。但由于开展的时间较短,今后在应用中该如何选择最佳方案、最佳时机以及减低移植物抗宿主病、移植相关死亡率及复发率等尚需进一步深入的研究。

BACKGROUND: Reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation(RIC-allo-HSCT) is proved being one of the effective methods to cure hematologic malignancies recently, which has been used more and more in patients with matched sibling or matched unrelated donor year by year. It is more suitable for elderly patients or younger patients combined with any organ dysfunction or complications. However, matched sibling and matched unrelated donors are not easy to be obtained for RIC-allo-HSCT. While HLA-haploidentical donor can be quickly found in family members for the patients who need receiving RIC-allo-HSCT. Fewer papers for reduced-intensity conditioning haploidentical hematopoietic stem cell transplantation(RIC-haplo-HSCT) have been reported in the world, and none in China, so the review for RIC-haplo-HSCT is necessary.OBJECTIVE: To reveiw the application of RIC-haplo-HSCT and its prospect.METHODS: Using 'nonmyeloablative conditioning, reduced intensity conditioning, HLA-haploidentical, hematopoietic stem cell transplantation' as key words, we retrieved Wanfang, CNKI and PubM ed databases, and foreign language search platform(1997-2014) by computer for literatures about RIC-haplo-HSCT. According to the inclusion and exclusion criteria, 25 articles in English were selected for our review ultimately.RESULTS AND CONCLUSION: This review shows that RIC-allo-HSCT with matched sibling and matched unrelated donor is widely used and has a better result increasingly. RIC-haplo-HSCT is carried out relatively late and less, and its engraftment, infection, transplant-related mortality, graft-versus-host disease, long-term disease-free survival and overall survival in the early period is a bit weak, but overall the situation has been recently improved significantly. Currently RIC-haplo-HSCT is feasible, especially for patients lack of matched sibling donor and matched unrelate donor, and HLA haploidentical donor becomes the most potential source of hematopoietic stem cells. RIC-haplo-HSCT retains strong graft-versus-leukemia effect, and is easy to look for donor, as well as there are sufficient cells for subsequent treatments such as donor lymphocyte infusion, which through a graft-versus-leukemia effect can eliminate the patient’s malignant cells, especially for elderly patients and younger patients combined with any organ dysfunction or complications. However, due to the relative short time to carry out RIC-haplo-HSCT, how to choice optimal RIC regimen and optimal opportunity and how to reduce transplant-related mortality,graft-versus-host disease and relapse rate require further in-depth studies.