Servais Sophie, Beguin Yves, Delens Loic, Ehx Grégory, Fransolet Gilles, Hannon Muriel, Willems Evelyne, Humblet-Baron Stéphanie, Belle Ludovic, Baron Frédéric
a Division of Hematology, Department of Medicine , University and CHU of Liège , Liège , Belgium.
b GIGA I3 , University of Liège , Liège , Belgium.
Expert Opin Investig Drugs. 2016 Aug;25(8):957-72. doi: 10.1080/13543784.2016.1182498. Epub 2016 May 9.
Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers potential curative treatment for a wide range of malignant and nonmalignant hematological disorders. However, its success may be limited by post-transplant acute graft-versus-host disease (aGVHD), a systemic syndrome in which donor's immune cells attack healthy tissues in the immunocompromised host. aGVHD is one of the main causes of morbidity and mortality after alloHSCT. Despite standard GVHD prophylaxis regimens, aGVHD still develops in approximately 40-60% of alloHSCT recipients.
In this review, after a brief summary of current knowledge on the pathogenesis of aGVHD, the authors review the current combination of a calcineurin inhibitor with an antimetabolite with or without added anti-thymocyte globulin (ATG) and emerging strategies for GVHD prevention.
A new understanding of the involvement of cytokines, intracellular signaling pathways, epigenetics and immunoregulatory cells in GVHD pathogenesis will lead to new standards for aGVHD prophylaxis allowing better prevention of severe aGVHD without affecting graft-versus-tumor effects.
异基因造血干细胞移植(alloHSCT)为多种恶性和非恶性血液系统疾病提供了潜在的治愈性治疗方法。然而,其成功可能受到移植后急性移植物抗宿主病(aGVHD)的限制,aGVHD是一种系统性综合征,其中供体的免疫细胞攻击免疫功能低下宿主中的健康组织。aGVHD是alloHSCT后发病和死亡的主要原因之一。尽管有标准的移植物抗宿主病预防方案,但仍有大约40%-60%的alloHSCT受者会发生aGVHD。
在本综述中,作者在简要总结当前关于aGVHD发病机制的知识后,回顾了目前钙调神经磷酸酶抑制剂与抗代谢物联合使用(加或不加抗胸腺细胞球蛋白(ATG))的情况以及预防移植物抗宿主病的新出现策略。
对细胞因子、细胞内信号通路、表观遗传学和免疫调节细胞在移植物抗宿主病发病机制中的作用的新认识将导致aGVHD预防的新标准,从而在不影响移植物抗肿瘤效应的情况下更好地预防严重aGVHD。