Negrin Robert S
Department of Medicine-Blood and Marrow Transplantation, Stanford University, Stanford, CA.
Hematology Am Soc Hematol Educ Program. 2015;2015:225-30. doi: 10.1182/asheducation-2015.1.225.
Graft-versus-host disease (GVHD) is a significant clinical problem after allogenic hematopoietic cell transplantation (HCT) associated with substantial morbidity and mortality that limits the potential utility of transplantation. Associated with GVHD is the well-recognized phenomenon of the graft-versus-leukemia (GVL) effect that results in reduced risk of disease relapse. GVL effects have been observed after treatment for a broad range of hematological malignancies. Both GVHD and GVL are the results of T cell-effector functions that frames a major question in the field of how linked are these two phenomena. A major goal of basic science and translational research has been to develop strategies to reduce the risk of GVHD while maintaining or enhancing GVL. In this review, a number of different strategies developed from preclinical animal models will be explored with a focus on those approaches that have been extended to the clinic in an attempt to achieve this goal. Needless to say, there is no proven strategy; however, with the use of modern technology and clinical translation, there has been substantial progress toward this goal of reducing the risks of GVHD while promoting and enhancing GVL responses.
移植物抗宿主病(GVHD)是异基因造血细胞移植(HCT)后一个严重的临床问题,与较高的发病率和死亡率相关,限制了移植的潜在效用。与GVHD相关的是公认的移植物抗白血病(GVL)效应现象,这会降低疾病复发风险。在对多种血液系统恶性肿瘤进行治疗后均观察到了GVL效应。GVHD和GVL都是T细胞效应功能的结果,这构成了该领域一个主要问题,即这两种现象的关联程度如何。基础科学和转化研究的一个主要目标是制定策略,在维持或增强GVL的同时降低GVHD风险。在本综述中,将探讨从临床前动物模型发展而来的一些不同策略,重点关注那些已扩展至临床的方法,以试图实现这一目标。不用说,目前尚无已证实的策略;然而,通过使用现代技术和临床转化,在降低GVHD风险同时促进和增强GVL反应这一目标上已取得了重大进展。