Srinagesh Hrishikesh K, Levine John E, Ferrara James L M
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Hess Center for Science and Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 6th Floor, New York, NY 10029, USA.
Ther Adv Hematol. 2019 Dec 4;10:2040620719891358. doi: 10.1177/2040620719891358. eCollection 2019.
Hematopoietic cell transplantation (HCT) is a potentially curative therapy for hematologic malignancies that relies on the graft--leukemia (GVL) effect to eradicate malignant cells. GVL is tightly linked to graft--host disease (GVHD) however, in which donor T cells damage healthy host tissues. Acute GVHD occurs in nearly 50% of patients receiving HCT, and damages the skin, liver, and gastrointestinal (GI) tract. The organ stages are totaled in an overall grade (I-IV), and severe (grade III/IV) GVHD has a high mortality rate (50-70%). In the past decade, serum biomarkers have emerged as an additional potential measurement of acute GVHD severity. The discovery and validation of GVHD biomarkers is a principal objective of the Mount Sinai Acute GVHD International Consortium (MAGIC), a group of 25 HCT centers conducting GVHD research. MAGIC has validated an algorithm that combines two GI biomarkers (ST2 and REG3α) into a single value that estimates the probability of 6 month nonrelapse mortality (NRM) for individual patients, known as the MAGIC algorithm probability (MAP). The MAP reflects GI crypt damage and serves as a 'liquid biopsy' of the lower GI tract; it also predicts response to treatment and maximum GVHD severity and is now commercially available and widely used among scores of centers in clinical practice. The MAP is the focus of this review, with consideration of the categorization of types of biomarkers as defined by the United States National Institutes of Health (NIH) and Food and Drug Administration (FDA).
造血细胞移植（HCT）是一种针对血液系统恶性肿瘤的潜在治愈性疗法，它依赖移植物抗白血病（GVL）效应来根除恶性细胞。然而，GVL与移植物抗宿主病（GVHD）紧密相关，在GVHD中，供体T细胞会损害健康的宿主组织。急性GVHD发生在近50%接受HCT的患者中，会损害皮肤、肝脏和胃肠道（GI）。器官阶段被汇总为一个总体分级（I - IV级），严重（III/IV级）GVHD有很高的死亡率（50 - 70%）。在过去十年中，血清生物标志物已成为急性GVHD严重程度的另一种潜在测量指标。GVHD生物标志物的发现和验证是西奈山急性GVHD国际联盟（MAGIC）的主要目标，该联盟由25个开展GVHD研究的HCT中心组成。MAGIC已经验证了一种算法，该算法将两种胃肠道生物标志物（ST2和REG3α）合并为一个单一值，用于估计个体患者6个月无复发生存率（NRM）的概率，即所谓的MAGIC算法概率（MAP）。MAP反映了胃肠道隐窝损伤，可作为下消化道的“液体活检”；它还能预测治疗反应和最大GVHD严重程度，目前已商业化并在众多临床实践中心广泛使用。MAP是本综述的重点，同时还考虑了美国国立卫生研究院（NIH）和食品药品监督管理局（FDA）所定义的生物标志物类型分类。
