[异基因造血干细胞移植后慢性移植物抗宿主疾病防治的最新进展]。

Tomomi Toubai, Yuka Hosokawa
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引用次数: 0

摘要

慢性移植物抗宿主疾病(cGVHD)对异基因造血细胞移植后的长期生存和生活质量(QOL)有负面影响。皮质类固醇是治疗 cGVHD 的一线疗法,但约 30% 至 70% 的患者会出现类固醇难治性 cGVHD(SR-cGVHD),预后极差。cGVHD 的病理生理学比急性 GVHD 更为复杂,但最近利用小鼠模型和人体研究取得的进展表明,cGVHD 主要分为三个阶段:1)急性炎症;2)慢性炎症,免疫耐受丧失;3)靶器官稳态紊乱和纤维化。有助于预防 cGVHD 的策略包括最佳供体选择、调理方案选择以及药物和移植物操作策略。SR-cGVHD的主要细胞介质是T细胞、B细胞、抗原递呈细胞和成纤维细胞。目前,T 细胞和 B 细胞可分别使用伊布替尼(ibrutinib)和鲁索利替尼(ruxolitinib)抑制剂。最近,通过使用 Rock2 抑制剂调节病理 T 细胞反应和使用 CSF-1R 抑制剂靶向纤维化,取得了令人鼓舞的成果。为了优化这些药物的使用,需要更好地了解cGVHD的生物学机制和靶器官特异性机制。在此,我们回顾了 cGVHD 发病机制的最新进展,并讨论了如何最好地实施最近批准的生物学驱动的 cGVHD 治疗。
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[Recent advances in prevention and treatment of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation].

Chronic graft-versus-host disease (cGVHD) negatively impacts long-term survival and quality of life (QOL) after allogeneic hematopoietic cell transplantation. Corticosteroids are the first-line treatment for cGVHD, but approximately 30% to 70% of patients develop steroid-refractory cGVHD (SR-cGVHD), which has an extremely poor prognosis. The pathophysiology of cGVHD is more complicated than acute GVHD, but recent advances using murine models in conjunction with human studies indicate three major phases: 1) acute inflammation, 2) chronic inflammation with loss of immune tolerance, and 3) disrupted target organ homeostasis and fibrosis. Strategies that help prevent cGVHD include optimal donor selection and choice of conditioning regimen as well as pharmacologic and graft manipulation strategies. The key cellular mediators of SR-cGVHD are T cells, B cells, antigen-presenting cells, and fibroblasts. T cells and B cells are now targetable with the inhibitors ibrutinib and ruxolitinib, respectively. Recently, promising results have been obtained by modulating pathologic T cell responses with Rock2 inhibitors and targeting fibrosis with CSF-1R inhibitors. To optimize the use of these medications, a better understanding of the biological and target organ-specific mechanisms of cGVHD is needed. Here we review recent advances in cGVHD pathogenesis and discuss how best to implement recently approved biology-driven treatments for cGVHD.

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