PDF(Pubmed)
Abstract：
Identifying plasma biomarkers early after allo-HCT may become crucial to prevent and treat severe aGvHD. We utilized samples from 203 allo-HCT patients selected from the Blood & Marrow Transplant Clinical Trials Network (BMT CTN) to identify new biomarker models to predict aGvHD and overall mortality. Two new biomarkers (Gal-3 and LAG-3), and previously identified biomarkers (ST2/IL33R, IL6, Reg3A, PD-1, TIM-3, TNFR1) were screened. Increased Gal-3 levels measured at Day +7 post-transplant predicted the development of aGvHD (grade 2-4) in the total population [AUC: 0.602; P = 0.045] while higher Day +14 levels predicted overall mortality due to toxicity among patients receiving reduced intensity conditioning [P = 0.028] but not myeloablative conditioning. Elevated LAG-3 levels (Day +21) were associated with less severe aGvHD [159.1 ng/mL vs 222.0 ng/mL; P = 0.046]. We developed a model utilizing Gal-3, LAG-3, and PD-1 levels at Days +14 and +21 with an improved performance to predict aGvHD and overall non-relapse mortality. We confirmed four informative biomarkers (Reg3A, ST2, TIM-3, and TNFR1) predict severe aGvHD at day +14 and day +21 (grade 3-4). In conclusion, the combination of Gal-3 alone or in combination with LAG-3, and PD-1 is a new informative model to predict aGvHD development and overall non-relapse mortality after allo-HCT.
摘要：
在allo-HCT后早期鉴定血浆生物标志物对于预防和治疗严重的aGvHD可能变得至关重要。我们利用从血液和骨髓移植临床试验网络（BMTCTN）中选择的203名allo-HCT患者的样本来识别新的生物标志物模型，以预测aGvHD和总死亡率。两个新的生物标志物（Gal-3和LAG-3），和先前鉴定的生物标志物(ST2/IL33R，IL6,Reg3A,筛选PD-1、TIM-3、TNFR1)。在移植后第7天测量的Gal-3水平的增加预测了总群体中aGvHD(2-4级)的发展[AUC:0.602;P=0.045],而第14天水平的较高预测了由于在接受降低的强度调节[P=0.028]但不是清髓性调节的患者中毒性引起的总死亡率。LAG-3水平升高（第21天）与较不严重的aGvHD相关[159.1ng/mLvs222.0ng/mL；P=0.046]。我们在第+14天和第+21天开发了利用Gal-3，LAG-3和PD-1水平的模型，具有预测aGvHD和总体非复发死亡率的改进性能。我们确认了四种信息生物标志物(Reg3A，ST2，TIM-3和TNFR1）在第14天和第21天（3-4级）预测严重的aGvHD。总之,Gal-3单独或与LAG-3和PD-1联合使用是预测allo-HCT后aGvHD发展和总体非复发死亡率的新信息模型.
