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

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.