Mattsson Jonas
Karolinska Institutet, Karolinska University Hospital, Center for Allogeneic Stem Cell Transplantation, Huddinge, SE-141 86 Stockholm, Sweden.
Curr Opin Mol Ther. 2008 Aug;10(4):343-9.
Allogeneic hematopoietic stem cell transplantation (ASCT) is a well-established treatment for patients with malignant and non-malignant immunohematopoietic diseases. Matched unrelated donors are increasingly used and improved HLA matching has led to increased survival. In addition, stem cells derived from peripheral blood and cord blood are being utilized to a greater extent. During the last decade, reduced-intensity conditioning, which is preferentially used in older patients or those with organ dysfunction, was introduced as an alternative to standard myeloablative regimens. In addition, the isolation of patients after transplant has been challenged by allowing patients to be treated at home after ASCT. Analysis of mutations in caspase recruitment domain containing protein 15 and levels of regulatory T-cells may be important in identifying patients at risk for acute graft-versus-host disease (GVHD). Mesenchymal stem cells that have immunomodulatory effects home in to injured tissues and may be used in the treatment of patients with steroid-refractory GVHD. In addition, the graft-versus-tumor (GVT) or graft-versus-leukemia (GVL) effect (ie, the attack of the transplanted immune system against the tumor or leukemia), is of major importance for the success of ASCT in patients with malignant disease. GVT and GVL effects may be improved by utilizing differences in minor histocompatibility antigens between the patients and the donor or by using natural killer cell alloreactivity. ASCT has shown GVT effects in patients with solid tumors. New developments in clinical ASCT have been highlighted in this review.
异基因造血干细胞移植(ASCT)是治疗恶性和非恶性免疫血液系统疾病患者的一种成熟疗法。越来越多地使用匹配的无关供体,改进的HLA配型提高了生存率。此外,外周血和脐带血来源的干细胞得到了更广泛的应用。在过去十年中,引入了强度降低的预处理方案,优先用于老年患者或有器官功能障碍的患者,作为标准清髓方案的替代方案。此外,允许患者在ASCT后在家中接受治疗,对移植后患者的隔离提出了挑战。分析含半胱天冬酶募集结构域蛋白15的突变和调节性T细胞水平,对于识别有急性移植物抗宿主病(GVHD)风险的患者可能很重要。具有免疫调节作用的间充质干细胞归巢至受损组织,可用于治疗对类固醇难治的GVHD患者。此外,移植物抗肿瘤(GVT)或移植物抗白血病(GVL)效应(即移植的免疫系统对肿瘤或白血病的攻击),对于恶性疾病患者ASCT的成功至关重要。利用患者与供体之间次要组织相容性抗原的差异或使用自然杀伤细胞同种异体反应性,可改善GVT和GVL效应。ASCT已在实体瘤患者中显示出GVT效应。本综述重点介绍了临床ASCT的新进展。