Inamoto Yoshihiro, Zeiser Robert, Chan Godfrey Chi-Fung
Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, Albert Ludwigs University (ALU), Freiburg, Germany.
Blood Cell Ther. 2021 Nov 25;4(4):101-109. doi: 10.31547/bct-2021-022.
Allogeneic hematopoietic cell transplantation is a curative therapy for a variety of hematological diseases, but its success is hampered by acute and chronic graft-versus-host disease (GvHD). In the last five years, multiple novel therapeutic approaches for GvHD have entered the arena. The National Institutes of Health consensus criteria for chronic GvHD have set standards for designing and reporting clinical trials, and preclinical experiments of chronic GvHD have revealed the central roles of regulatory T cells, B-cell signaling, Th17 cells, Tc17 cells, follicular helper T cells, follicular regulatory T cells, and fibrosis-promoting factors. These scientific efforts and the resulting clinical studies led to the approval of ibrutinib, belumosudil and ruxolitinib for the treatment of refractory chronic GvHD. Recently, large randomized phase III trials showed that ruxolitinib was superior to the best available therapy for glucocorticoid-refractory acute GvHD (REACH2 trial) and glucocorticoid-refractory chronic GvHD (REACH3 trial). Furthermore, novel regenerative approaches, including IL-22, R-spondin, and glucogon-like peptide-2, and cellular therapies, such as the transfer of mesenchymal stem cells and regulatory T cells, are under intensive investigation. GvHD prevention using abatacept, dipeptidyl peptidase 4 inhibition, and post-transplant cyclophosphamide are also promising strategies that require further evaluation. In this article, we summarize the emerging knowledge of acute GvHD, chronic GvHD, and preclinical and clinical data of mesenchymal stem cells as GvHD therapy. In the next five years, basic and clinical studies will further advance the field, and dramatic changes in GvHD management will be encountered.
异基因造血细胞移植是治疗多种血液系统疾病的一种根治性疗法，但其成功率受到急性和慢性移植物抗宿主病（GvHD）的阻碍。在过去五年中，多种针对GvHD的新型治疗方法已进入临床应用。美国国立卫生研究院关于慢性GvHD的共识标准为设计和报告临床试验设定了标准，慢性GvHD的临床前实验揭示了调节性T细胞、B细胞信号传导、Th17细胞、Tc17细胞、滤泡辅助性T细胞、滤泡调节性T细胞和促纤维化因子的核心作用。这些科学努力以及由此产生的临床研究使得伊布替尼、贝利司他和芦可替尼获批用于治疗难治性慢性GvHD。最近，大型随机III期试验表明，芦可替尼在治疗糖皮质激素难治性急性GvHD（REACH2试验）和糖皮质激素难治性慢性GvHD（REACH3试验）方面优于现有最佳疗法。此外，包括白细胞介素-22、R-spondin和胰高血糖素样肽-2在内的新型再生方法以及细胞疗法，如间充质干细胞和调节性T细胞的移植，正在深入研究中。使用阿巴西普、二肽基肽酶4抑制剂和移植后环磷酰胺预防GvHD也是有前景的策略，需要进一步评估。在本文中，我们总结了急性GvHD、慢性GvHD的最新知识以及间充质干细胞作为GvHD治疗方法的临床前和临床数据。在未来五年中，基础和临床研究将进一步推动该领域的发展，GvHD的管理将发生巨大变化。
