Division of Hematologic Malignancies, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Expert Rev Hematol. 2008 Oct;1(1):111. doi: 10.1586/17474086.1.1.111.
Graft-versus-host disease (GVHD), both acute and chronic, remains one of the major barriers to improving outcomes after allogeneic stem cell transplantation. The pathophysiology of GVHD is complex and incompletely understood. GVHD is believed to arise from the interaction of: tissue damage and proinflammatory cytokines causing activation of antigen-presenting cells (APCs, donor T-cell activation by APCs and cytokines and host tissue injury by effector T lymphocytes and proinflammatory cytokines. There is also a role for additional lymphocyte subtypes (naive and memory T cells, regulatory T cells, natural killer T cells and B cells) in GVHD pathogenesis. Strategies to improve donor-recipient HLA match, and to minimize conditioning toxicity, cytokine release and APC and effector T-lymphocyte activation, will likely improve prophylaxis of acute (and possibly chronic) GVHD. Therapy of established acute and chronic GVHD is still heavily dependent on corticosteroids, despite their limited efficacy and considerable toxicity. Novel agents (and/or combinations of agents) comprising pharmacologic, biologic and cellular therapies targeting specific steps or subsets involved in immune activation will likely comprise future advances in GVHD control. This article reviews the current state of knowledge regarding the prevention and treatment of acute and chronic GVHD. Novel approaches currently undergoing evaluation are also highlighted.
移植物抗宿主病（GVHD），包括急性和慢性 GVHD，仍然是影响异基因造血干细胞移植后患者转归的主要障碍之一。GVHD 的发病机制复杂且尚未完全阐明。目前认为 GVHD 是由以下因素相互作用引起的：组织损伤和促炎细胞因子导致抗原呈递细胞（APC）的激活，APC 和细胞因子激活供者 T 细胞，效应 T 淋巴细胞和促炎细胞因子导致宿主组织损伤。此外，其他淋巴细胞亚群（初始和记忆 T 细胞、调节性 T 细胞、自然杀伤 T 细胞和 B 细胞）在 GVHD 发病机制中也发挥作用。提高供者和受者 HLA 匹配度、降低预处理毒性、细胞因子释放以及 APC 和效应 T 淋巴细胞激活的策略，可能会改善急性（和可能的慢性）GVHD 的预防。尽管皮质类固醇疗效有限且毒性较大，但治疗已确立的急性和慢性 GVHD 仍然严重依赖皮质类固醇。针对免疫激活特定步骤或亚群的新型药物（和/或药物联合）包括药理学、生物学和细胞疗法，可能会成为 GVHD 控制的未来进展。本文综述了目前关于急性和慢性 GVHD 的预防和治疗的知识现状。同时还强调了正在评估的新型方法。
