Prognostic plasma biomarkers of early complications and graft-versus-host disease in patients undergoing allogeneic hematopoietic stem cell transplantation

异基因造血干细胞移植患者早期并发症和移植物抗宿主病的预后血浆生物标志物

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作者:Balaji Balakrishnan, Raveen Stephen Stallon Illangeswaran, Bharathi M Rajamani, Aswin Anand Pai, Infencia Xavier Raj, Daniel Zechariah Paul, Kavitha Lakshmi, Thenmozhi Mani, Ezhilpavai Mohanan, Uday Kulkarni, Anup Joseph Devasia, N A Fouzia, Anu Korula, Aby Abraham, Alok Srivastava, Vikram Mathews, 

Abstract

Early complications post hematopoietic stem cell transplantation (HSCT) such as sinusoidal obstruction syndrome (SOS) and graft versus host disease (GVHD) can be life threatening. Although several biomarkers have been identified to correlate with these complications and their response to treatment, these are yet to be used in clinical practice. Here, we evaluated circulating endothelial cells (CECs) (n = 26) and plasma biomarkers (ST2, REG3α, VCAM1, ICAM1, TIM3) (N = 210) at early time points, to determine their association with early complications post-HSCT. Elevated CEC counts at the end of conditioning was associated with GVHD, indicating endothelial damage during HSCT. Plasma levels of REG3α, VCAM1, ICAM1, and TIM3 on day 14 (D14) and D14 ICAM1 and D28 ST2 were significantly higher in patients with SOS and aGVHD, respectively. Upon sub-group analysis, D28 ST2, D14/D28 REG3α, and D14ICAM1 levels were significantly higher in patients with gastrointestinal GVHD, while D28ST2 was higher in those with skin/liver GVHD. High ST2 levels on D28 was significantly associated with non-relapse mortality (NRM) and overall survival. Our results suggest that elevated ST2 levels on D28 could predict the likelihood of developing aGVHD and could influence NRM and OS.

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