Nakasone Hideki, Sahaf Bita, Miklos David B
Division of Blood and Marrow Transplantation, Stanford University School of Medicine, 269 West Campus Dr., CCSR #2205, Stanford, CA, 94305, USA.
Int J Hematol. 2015 May;101(5):438-51. doi: 10.1007/s12185-015-1782-4. Epub 2015 Mar 27.
Allogeneic hematopoietic cell transplantation (allo-HCT) can be a curative strategy for hematological diseases, and the indications for allo-HCT have broadened widely due to recent progress in supportive strategies. However, patients must overcome various complications and chronic graft-versus-host disease (cGVHD) remains the most common allo-HCT cause of long-term morbidity and mortality. cGVHD is difficult to biologically assess due to the heterogeneity of cGVHD symptoms, and the pathogenesis of cGVHD has yet to be established. Recent experimental model progress has suggested that B-cells play a critical role in cGVHD development. Consistent with these experimental results, some clinical studies investigating B-cell depletion and modulation of B-cell signaling pathways have decreased cGVHD incidence and provided some therapeutic benefit. However, randomized control studies are necessary to confirm the efficacy of B-cell targeting drugs for cGVHD. Here, we review the pathophysiology of cGVHD, especially focusing on the role of B-cell immunity, and discuss the efficacy of both B-cell depletion and modulation of B-cell signaling pathways in human cGVHD prevention, initial treatment, and salvage treatment.
异基因造血细胞移植（allo-HCT）可以作为治疗血液系统疾病的一种治愈性策略，并且由于支持性策略的最新进展，allo-HCT的适应症已广泛扩大。然而，患者必须克服各种并发症，慢性移植物抗宿主病（cGVHD）仍然是allo-HCT导致长期发病和死亡的最常见原因。由于cGVHD症状的异质性，cGVHD难以进行生物学评估，并且cGVHD的发病机制尚未明确。最近实验模型的进展表明，B细胞在cGVHD的发展中起关键作用。与这些实验结果一致，一些研究B细胞清除和B细胞信号通路调节的临床研究降低了cGVHD的发生率，并提供了一些治疗益处。然而，需要进行随机对照研究来证实B细胞靶向药物对cGVHD的疗效。在此，我们综述cGVHD的病理生理学，尤其关注B细胞免疫的作用，并讨论B细胞清除和B细胞信号通路调节在人类cGVHD预防、初始治疗和挽救治疗中的疗效。
