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移植物抗宿主病生物标志物:组学和个性化医学。

Graft-versus-host disease biomarkers: omics and personalized medicine.

出版信息

Int J Hematol. 2013 Sep;98(3):275-92. doi: 10.1007/s12185-013-1406-9.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective form of tumor immunotherapy available to date and the frequency of transplants continues to increase worldwide. However, while allo-HSCT usually induces a beneficial graft-versus leukemia effect, a major source of morbidity and mortality following allo-HSCT is graft-versus-host disease (GVHD). Currently available diagnostic and staging tools frequently fail to identify those at higher risk for GVHD morbidity, treatment unresponsiveness, and death. Furthermore, there are shortcomings in the risk stratification of patients before GVHD clinical signs develop. In parallel, recent years have been characterized by an explosive evolution of omics technologies, largely due to technological advancements in chemistry, engineering, and bioinformatics. Building on these opportunities, plasma biomarkers have been identified and validated as promising diagnostic and prognostic tools for acute GVHD. This review summarizes current information on the types of GVHD biomarkers, the omics tools used to identify them, the biomarkers currently validated as acute GVHD markers, and future recommendations for incorporating biomarkers into new grading algorithms for risk-stratifying patients and creating more personalized treatment courses. Future directions will include randomized evaluations of these biomarkers in multicenter prospective studies while extending on the need for biomarkers of chronic GVHD.

摘要

异基因造血干细胞移植(allo-HSCT)是迄今为止最有效的肿瘤免疫治疗形式,全球移植的频率持续增加。然而,尽管 allo-HSCT 通常会诱导有益的移植物抗白血病效应,但 allo-HSCT 后发病率和死亡率的主要来源是移植物抗宿主病(GVHD)。目前可用的诊断和分期工具经常无法识别那些患有 GVHD 发病率、治疗无反应和死亡风险较高的患者。此外,在 GVHD 临床症状出现之前,患者的风险分层存在缺陷。与此同时,近年来,由于化学、工程和生物信息学方面的技术进步,组学技术呈爆炸式发展。在此基础上,血浆生物标志物已被确定并验证为急性 GVHD 的有前途的诊断和预后工具。这篇综述总结了目前关于 GVHD 生物标志物类型、用于识别它们的组学工具、目前已验证为急性 GVHD 标志物的生物标志物,以及将生物标志物纳入新的风险分层算法以对患者进行风险分层和制定更个性化的治疗方案的未来建议。未来的方向将包括在多中心前瞻性研究中对这些生物标志物进行随机评估,同时需要对慢性 GVHD 的生物标志物进行扩展。

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