El Jurdi Najla, Blazar Bruce R, Pavletic Steven Z
Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Department of Pediatrics, Division of Blood and Marrow Transplant and Cellular Therapy, University of Minnesota, Minneapolis, MN.
Transplantation. 2025 Feb 7. doi: 10.1097/TP.0000000000005345.
Chronic graft-versus-host disease (cGVHD) is an immune-mediated, heterogeneous, multiorgan complication affecting allogeneic hematopoietic cell transplantation recipients, leading to increased morbidity, mortality, and decline in health-related quality-of-life. Advances in understanding the complex disease pathophysiology, and collaborative efforts lead by the National Institutes of Health to standardize criteria for clinical trials, led to bench-to-bedside efforts resulting in the development of 4 US Food and Drug Administration-approved agents for the treatment steroids-refractory cGVHD since 2017. Despite the remarkable advances in the field of hematopoietic cell transplantation in prevention of cGVHD, and more treatment options, the outcome of patients with moderate-severe cGVHD remains suboptimal. Essential to successful cGVHD management is to recognize the disease at early stages before the onset of irreversible damage, allowing for personalized multidisciplinary specialized interventions that include pharmacologic therapies and additional supportive care measures. The aim of this review is to summarize key areas of active clinical research and new developments in cGVHD therapeutic approaches, with focus on (1) preemptive therapy, (2) upfront therapy beyond corticosteroids, (3) treatment refractory cGVHD novel agents, role of combination therapies, and organ-specific approaches, and (4) challenges, gaps, and future directions.
慢性移植物抗宿主病（cGVHD）是一种免疫介导的、异质性的多器官并发症，影响异基因造血细胞移植受者，导致发病率和死亡率增加以及健康相关生活质量下降。在理解这种复杂疾病的病理生理学方面取得的进展，以及美国国立卫生研究院牵头的标准化临床试验标准的合作努力，促成了从 bench 到 bedside 的工作，自2017年以来开发出了4种获得美国食品药品监督管理局批准用于治疗类固醇难治性 cGVHD 的药物。尽管在造血细胞移植领域预防 cGVHD 取得了显著进展，且有更多治疗选择，但中重度 cGVHD 患者的治疗结果仍不尽人意。成功管理 cGVHD 的关键在于在不可逆转的损害发生之前的早期阶段识别该疾病，以便进行个性化的多学科专业干预，包括药物治疗和其他支持性护理措施。本综述的目的是总结 cGVHD 治疗方法中积极的临床研究关键领域和新进展，重点关注（1）抢先治疗，（2）皮质类固醇之外的初始治疗，（3）治疗难治性 cGVHD 的新型药物、联合治疗的作用和器官特异性方法，以及（4）挑战、差距和未来方向。
