A prognostic score for acute graft-versus-host disease based on biomarkers: a multicentre study.
A prognostic score for acute graft-versus-host disease based on biomarkers: a multicentre study.
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DOI：
10.1016/s2352-3026(14)00035-0
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发表时间：
2015-01
影响因子：
24.7
通讯作者：
Ferrara, James L. M.
中科院分区：
文献类型：
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作者：
Levine, John E.;Braun, Thomas M.;Harris, Andrew C.;Holler, Ernst;Taylor, Austin;Miller, Holly;Magenau, John;Weisdorf, Daniel J.;Ho, Vincent T.;Bolanos-Meade, Javier;Alousi, Amin M.;Ferrara, James L. M.
移植物抗宿主病（GVHD）是异基因造血干细胞移植（HCT）后非复发性死亡（NRM）的主要原因。GVHD发作时症状的严重程度不能准确定义风险，因此大多数患者都用高剂量全身性皮质类固醇治疗。我们的目的是使用血浆生物标志物定义新诊断急性GVHD患者的临床有意义的风险分层。我们前瞻性地收集了492例新诊断急性GVHD的HCT患者的血浆，并将其随机分为训练组（n=328）和测试组（n=164）。我们使用三种最近验证的生物标志物（TNFR 1，ST 2和REG 3 α）的浓度来创建一种算法，该算法计算了单独训练集中个体患者GVHD发作后6个月NRM的概率。我们对概率进行了排序，并确定了创建三个不同NRM分数的阈值。我们在测试集中评估了该算法，并再次在一个独立的验证集中评估了300例额外的HCT患者，这些患者参加了急性GVHD主要治疗的多中心临床试验。在所有三个数据集中，随着GVHD评分的增加，12个月NRM的累积发生率显著增加（8% [95%置信区间（CI）; 3%，16%]，27% [95% CI; 20%，34%]和46% [95% CI; 33%，58%]，在多中心验证集中分别为1、2和3分，p<0 · 0001）。相反，原发性GVHD治疗的应答率随着GVHD评分的增加而降低（多中心验证组中，评分1、2和3分别为86%、67%和46%，p<0.0001）。基于生物标志物的评分可用于指导急性GVHD发作时的风险适应性治疗。
Graft-versus-host disease (GVHD) is the major cause of non-relapse mortality (NRM) after allogeneic hematopoietic stem-cell transplantation (HCT). The severity of symptoms at the onset of GVHD does not accurately define risk, and thus most patients are treated alike with high dose systemic corticosteroids. We aimed to define clinically meaningful risk strata for patients with newly diagnosed acute GVHD using plasma biomarkers. We prospectively collected plasma from 492 HCT patients with newly diagnosed acute GVHD and randomly divided them into training (n=328) and test (n=164) sets. We used the concentrations of three recently validated biomarkers (TNFR1, ST2, and REG3α) to create an algorithm that computed the probability of NRM six months after GVHD onset for individual patients in the training set alone. We rank ordered the probabilities and identified thresholds that created three distinct NRM scores. We evaluated the algorithm in the testset, and again in an independent validation set of 300 additional HCT patients enrolled on multicenter clinical trials of primary therapy for acute GVHD. In all three datasets, the cumulative incidence of twelve month NRM significantly increased as the GVHD score increased (8% [95% confidence interval (CI); 3%, 16%], 27% [95% CI; 20%%, 34%], and 46% [95% CI; 33%, 58%], for scores 1, 2 and 3 respectively in the multicenter validation set, p<0 · 0001). Conversely, the response rates to primary GVHD treatment decreased as the GVHD score increased (86%, 67%, and 46%, for scores 1, 2 and 3 respectively in the multicenter validation set, p<0 · 0001). Biomarker-based scores can be used to guide risk-adapted therapy at the onset of acute GVHD.