从机制到临床:慢性移植物抗宿主病的诊疗进展与挑战

From mechanism to clinical practice: advances and challenges in the diagnosis and treatment of chronic graft-versus-host disease

  • 摘要: 慢性移植物抗宿主病(cGVHD)是异基因造血干细胞移植后最常见的晚期并发症,发生率为30%~70%,严重影响患者长期生存。该病临床表现异质性强,可累及皮肤、口腔、眼、肺、肝等多器官,其核心机制涉及慢性炎症、免疫耐受破坏及T、B细胞失调,最终导致组织纤维化。近年来,随着发生机制研究的深化,cGVHD治疗已从传统糖皮质激素,发展为针对JAK、ROCK2、BTK等关键信号通路的靶向药物、耗竭致病免疫细胞的生物制剂,以及重建免疫耐受的细胞疗法,形成多元化、精准化治疗新格局。本文综述了cGVHD在流行病学、发生机制、诊断评估与治疗策略方面的进展。现有证据提示,针对纤维化与免疫耐受的联合及序贯治疗,是突破当前cGVHD治疗瓶颈的关键方向。

     

    Abstract: Chronic graft-versus-host disease (cGVHD) is the most common late complication after allogeneic hematopoietic stem cell transplantation, with an incidence rate of 30% to 70%. It significantly affects the long-term survival of patients. The clinical manifestations of this disease are highly heterogeneous and can involve multiple organs such as the skin, mouth, eyes, lungs and liver. Its core mechanism involves chronic inflammation, disruption of immune tolerance and dysregulation of T and B cells, ultimately leading to tissue fibrosis. In recent years, with the deepening of research on the pathogenesis, the treatment of cGVHD has evolved from traditional glucocorticoids to targeted drugs targeting key signaling pathways such as JAK, ROCK2 and BTK, biological agents that deplete pathogenic immune cells, and cell therapies for reestablishing immune tolerance, forming a diversified and precise treatment landscape. This article reviews the progress in the epidemiology, pathogenesis, diagnostic assessment and treatment strategies of cGVHD. Current evidence suggests that combined and sequential treatment targeting fibrosis and immune tolerance is a key direction for breaking through the current treatment bottleneck of cGVHD.

     

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