Soluble Thrombomodulin Is Associated With Endothelial Dysfunction Syndromes After Pediatric Hematopoietic Stem Cell Transplantation

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by endothelial dysfunction-related syndromes like sinusoidal obstruction syndrome (SOS), capillary leak syndrome (CLS), and severe acute graft-versus-host disease (aGvHD). We investigated soluble thrombomodulin (sTM), an endothelial damage marker, in relation to endothelial dysfunction syndromes after pediatric HSCT. Procedure: We measured sTM levels in 113 children before conditioning until Day +180 after HSCT. Results: Plasma levels of sTM increased significantly after conditioning, particularly in patients receiving busulfan-based regimens (Day +7: 5.0 vs. 7.6 ng/mL, p = 0.0023), and remained elevated until Day +180 after HSCT. Children diagnosed with SOS (n = 51) had significantly higher sTM levels at Days +7 and +14 than children without SOS (Day +7: 7.3 vs. 5.0 ng/mL, p = 0.017). High sTM levels at Day +14 were associated with aGvHD Grade III–IV (n = 8) in multivariable analysis (OR = 3.0 per quartile increase in sTM, p = 0.021). Likewise, children diagnosed with CLS (n = 15) displayed higher sTM levels at Day +7 (5.3 vs. 8.0 ng/mL, p = 0.037), while sTM levels were not associated with engraftment syndrome or bacteremia. Conclusion: High sTM levels early after pediatric HSCT are associated with the development of SOS, CLS, and severe aGvHD. These results suggest that conditioning-induced endothelial damage and activation of pro-thrombotic environment play key roles in the pathogenesis of these syndromes, indicating that sTM may prove clinically useful to guide early diagnosis and treatment of endothelial damage syndromes.