Abstract
Objective:A soluble form of suppression of tumorigenicity 2 (sST2) has emerged as a biomarker for acute graft-versus-host disease (GVHD) and non-relapse mortality (NRM). We prospectively monitored sST2 levels during the early phase of hematopoietic stem cell transplantation (HSCT) and evaluated the clinical association with transplant-related complications including acute GVHD.Materials and Methods:Thirty-two adult Japanese patients who received a first allogeneic HSCT were enrolled in this study. Levels of sST2 were measured at fixed time points (pre-conditioning, day 0, day 14, day 21, and day 28).Results:The median age was 50.5 years (range=16-66). With a median follow-up of 21.5 months (range=0.9-35.4), 9 patients developed grade II-IV acute GVHD. Median sST2 levels on the day of HSCT were higher than baseline and reached the maximum value (92.7 ng/mL; range=0-419.7) on day 21 after HSCT. The optimal cut-off value of sST2 on day 14 for predicting grade II-IV acute GVHD was determined as 100 ng/mL by ROC analysis. The cumulative incidence of acute GVHD was 56.7% and 16.5% in the high- and low-sST2 groups, respectively (p<0.01). Multivariate analyses showed that high sST2 levels at day 14 were associated with a higher incidence of acute GVHD (hazard ratio=9.35, 95% confidence interval=2.92-30.0, p<0.01). The cumulative incidence of NRM was increased in the high-sST2 group (33% vs 0%, p<0.01), but all the patients died of non-GVHD complications. Among 6 patients in the high-sST2 group without grade II-IV GVHD, 5 patients developed veno-occlusive disease (VOD) and one also had thrombotic microangiopathy (TMA).Conclusion:The early assessment of sST2 after HSCT yielded predictive values for the onset of acute GVHD and other transplant-related complications including VOD and TMA.
Highlights
Acute graft-versus-host disease (GVHD) is one of the major complications after allogeneic hematopoietic stem cell transplantation (HSCT) and remains the leading cause of nonrelapse mortality (NRM) [1,2]
The optimal cutoff value of soluble form of suppression of tumorigenicity 2 (ST2) (sST2) on day 14 for predicting grade II-IV acute GVHD was determined as 100 ng/mL by receiver operating characteristics (ROC) analysis
The cumulative incidence of NRM was increased in the highsST2 group (33% vs 0%, p
Summary
Acute graft-versus-host disease (GVHD) is one of the major complications after allogeneic hematopoietic stem cell transplantation (HSCT) and remains the leading cause of nonrelapse mortality (NRM) [1,2]. Recent studies show several plasma biomarkers that correlate with acute GVHD: suppression of tumorigenicity 2 (ST2) [3,4], interleukin (IL)-2 receptor α [5], tumor necrosis factor receptor 1 (TNFR1) [5], hepatocyte growth factor [5], IL-8 [5], and IL-6 [6] for systemic GVHD; elafin for skin GVHD [7]; and regenerating islet-derived 3-α [8] and T-cell immunoglobulin mucin-3 for gastrointestinal GVHD [8,9,10,11,12]. Among these biomarkers, ST2 has emerged as a promising biomarker for onset or steroid-resistant acute GVHD and NRM [3,4,12,13,14]. The ST2/IL-33 axis has been reported as a potential therapeutic target for GVHD [20,21]
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