Zhang Cheng, Zhang Xi, Chen Xing-Hua
Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, People's Republic of China.
Transfus Apher Sci. 2013 Feb;48(1):3-9. doi: 10.1016/j.transci.2012.08.004. Epub 2012 Dec 29.
Despite improvements in transplant immunology and clinical and supportive care, acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major cause of morbidity and mortality for patients after allogeneic hematopoietic stem cell transplantation (HSCT). Many ways have been used to prevent and treat aGVHD, however, long-term survival remains poor. The key to improve aGVHD outcomes may, in fact, rest upon successful initial therapy. The HLA-matched HSCT was limited by the shortage of suitable donors. Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells and G-CSF-mobilized bone marrow as a stronger aGVHD inhibition and graft-versus-leukemia effect, has been developed as an alternative transplantation strategy for patients with hematologic malignancies for the advantage of immediate donor availability, ability to select the best of many relatives, controlled graft composition and immediate access to donor-derived cellular therapies if required after transplantation. G-CSF is a potent hematopoietic cytokine, which is produced by fibroblasts, monocytes, and endothelial cells. G-CSF regulates production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation, maturation and is also involved in mobilization of granulocytes, stem and progenitor cells, which has an important role in this transplantation. In this article, we review the possible mechanism for this combined G-CSF-mobilized HSCT in the prevention of aGVHD. Monocytes, T cells, Tregs cells, DC, adhesive molecule, NK cell/KIR ligand mismatching and mesenchymal stem cells may be involved in this transplantation.
尽管移植免疫学以及临床和支持治疗有所改善,但急性移植物抗宿主病(aGVHD)仍然是一个临床挑战,并且是异基因造血干细胞移植(HSCT)后患者发病和死亡的主要原因。已经采用了多种方法来预防和治疗aGVHD,然而,长期生存率仍然很低。事实上,改善aGVHD治疗结果的关键可能在于初始治疗的成功。HLA匹配的HSCT受到合适供体短缺的限制。未处理的单倍体相合/不相合相关移植联合粒细胞集落刺激因子(G-CSF)动员的外周血干细胞和G-CSF动员的骨髓,具有更强的aGVHD抑制和移植物抗白血病作用,已被开发为血液系统恶性肿瘤患者的替代移植策略,其优势在于供体可立即获得、能够从众多亲属中选择最佳供体、可控制移植物组成以及移植后如有需要可立即获得供体来源的细胞治疗。G-CSF是一种有效的造血细胞因子,由成纤维细胞、单核细胞和内皮细胞产生。G-CSF调节骨髓中中性粒细胞的生成,并影响中性粒细胞祖细胞的增殖、成熟,还参与粒细胞、干细胞和祖细胞的动员,这在这种移植中具有重要作用。在本文中,我们综述了这种联合G-CSF动员的HSCT预防aGVHD的可能机制。单核细胞、T细胞、调节性T细胞、树突状细胞、黏附分子、自然杀伤细胞/杀伤细胞免疫球蛋白样受体配体错配以及间充质干细胞可能参与了这种移植。