Prediction of acute GVHD and relapse by metabolic biomarkers after allogeneic hematopoietic stem cell transplantation
Xiaojin Wu, Yiyu Xie, Chang Wang, Yue Han, Xiebing Bao, Shoubao Ma, Ahmet Yilmaz, Bingyu Yang, Yuhan Ji, Jinge Xu, Hong Liu, Suning Chen, Jianying Zhang, Jianhua Yu, Depei Wu
Xiaojin Wu, Yiyu Xie, Chang Wang, Yue Han, Xiebing Bao, Shoubao Ma, Ahmet Yilmaz, Bingyu Yang, Yuhan Ji, Jinge Xu, Hong Liu, Suning Chen, Jianying Zhang, Jianhua Yu, Depei Wu
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Clinical Research and Public Health Hematology

Prediction of acute GVHD and relapse by metabolic biomarkers after allogeneic hematopoietic stem cell transplantation

Abstract

BACKGROUND. There are very few studies investigating metabolic biomarkers to predict acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Metabolic models can provide a framework for analyzing the information-rich omics data sets in this setting. METHODS. Four hundred and fifty-six samples from one hundred and fourteen consecutive patients who underwent HSCT from January 2012 to May 2014 were collected for this study. The changes in serum metabolite levels were investigated using a gas chromatography–mass spectrometry–based metabolomics approach and underwent statistical analysis. RESULTS. Significant metabolic changes were observed on day 7. The stearic acid/palmitic acid (SA/PA) ratio was effective in the diagnosis of grade II–IV aGVHD. Multivariate analysis showed that patients with high SA/PA ratios on day 7 after HSCT were less likely to develop II–IV aGVHD than patients with low SA/PA ratios (odds ratio [OR] = 0.06, 95% CI 0.02–0.18, P < 0.001). After the adjustment for clinical characteristics, the SA/PA ratio had no significant effect on overall survival (hazard ratio [HR] = 1.95, 95% CI 0.92–4.14, P = 0.08), and patients in the high SA/PA ratio group were significantly more likely to relapse than those in the low ratio group (HR = 2.26, 95% CI 1.04–4.91, P = 0.04). CONCLUSION. Our findings suggest that the SA/PA ratio on day 7 after HSCT is an excellent biomarker to predict both aGVHD and relapse. The serum SA/PA ratio measured on day 7 after transplantation may improve risk stratification for aGVHD and relapse after allogeneic stem cell transplantation. FUNDING. National Natural Science Foundation of China (81470346, 81773361), Priority Academic Program Development of Jiangsu Higher Education Institutions, Jiangsu Natural Science Foundation (BK20161204), Innovation Capability Development Project of Jiangsu Province (BM2015004), Jiangsu Medical Junior Talent Person award (QNRC2016707), and NIH (AI129582 and NS106170).

Authors

Xiaojin Wu, Yiyu Xie, Chang Wang, Yue Han, Xiebing Bao, Shoubao Ma, Ahmet Yilmaz, Bingyu Yang, Yuhan Ji, Jinge Xu, Hong Liu, Suning Chen, Jianying Zhang, Jianhua Yu, Depei Wu

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Figure 1

Study scheme of discovery and validation.

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Study scheme of discovery and validation. Clinical data and serum sample...
Clinical data and serum samples after hematopoietic stem cell transplantation were available from 114 patients transplanted at The First Affiliated Hospital of Soochow University. Serum samples were collected on days –9, 0, 7, and 14 after transplantation. We randomly selected 13 patients with 0–I aGVHD and 15 with II–IV aGVHD to set up a discovery set. The rest of the patients (59 with aGVHD 0–I and 27 with II–IV aGVHD) were included in the validation set. Our metabolic analyses always began with the discovery set. Significant metabolic changes were observed on day 7 (P < 0.001). The ratio of two metabolites (stearic acid/palmitic acid [SA/PA]) was considered as a single biomarker. Logistic regression, Cox regression, competing-risks regression, and leave-one-out cross-validation were used to evaluate the association of the potential metabolites with the occurrence of aGVHD, overall survival, progress-free survival, relapse, and mortality without relapse.