Increased Plasma ST2 Levels Precede the Development of Severe Acute GvHD and Chronic GvHD After Pediatric Hematopoietic Stem Cell Transplantation

Abstract

Background

The suppressor of tumorigenesis 2 (ST2) has emerged as one of the most promising biomarkers for predicting mortality of acute graft-versus-host disease (aGvHD) when measured at the onset of symptoms, but detailed time course studies are needed to understand the potential of ST2 as a risk marker of both aGvHD and chronic graft-versus-host disease (cGvHD), potentially allowing pre-emptive adjustment of immunosuppressive treatment.

Procedure

We measured ST2 levels in 117 children undergoing standard hematopoietic stem cell transplantation (HSCT) before conditioning and at regular intervals post-HSCT.

Results

ST2 levels were significantly increased from Day +7 in patients developing aGvHD of any grade (no GvHD: 23.6 ng/mL; Grade I: 31.9 ng/mL; Grade II: 33.2 ng/mL; Grade III–IV: 59.1 ng/mL; p < 0.0001) and in patients developing aGvHD with visceral involvement (no GvHD: 23.6 ng/mL; skin only aGvHD: 24.9 ng/mL; GI and/or liver aGvHD: 59.8 ng/mL; p < 0.0001). The association between ST2 levels and aGvHD Grade II–IV was confirmed in a multivariable logistic regression analysis, adjusting for diagnosis, conditioning regimen, and donor type (OR = 1.99 per doubling in ST2, 95% confidence interval [CI] = 1.40–2.92; p = 0.00025). Patients developing cGvHD had significantly higher ST2 levels before conditioning and from Day +21 to Day +180 (all p < 0.05). ST2 levels at Day +90 were significantly associated with later development of cGvHD after adjusting for diagnosis, conditioning regimen, donor type, and prior aGvHD (HR = 2.1 per doubling in ST2, 95% CI = 1.51–2.91, p < 0.0001).

Conclusion

This study confirms ST2 as a biomarker reflecting risk of aGvHD and prognosis in pediatric allogeneic HSCT, and our findings indicate a role of ST2 as an early risk marker of cGvHD.