Detecting Endothelial Compromise Objectively through Dynamic EASIX Scoring (DECODE) - Predictive Utility of EASIX and Modified EASIX Scores for Endothelial Complications Post Hematopoietic Cell Transplant

Saad Ghafoor^1,2*Kimberly Uchida^3,4Yvonne Avent¹Chia-Wei Hsu¹Haitao Pan¹LAMA ELBAHLAWAN^1*

• ¹St. Jude Children's Research Hospital, Memphis, United States
• ²The University of Tennessee Health Science Center, Memphis, United States
• ³University of Utah Hospital, Salt Lake City, United States
• ⁴Intermountain Health, Salt Lake City, United States

Introduction Endothelial injury is a major contributor to morbidity and mortality in pediatric patients undergoing hematopoietic cell transplantation (HCT). It appears as sinusoidal obstruction syndrome (SOS) or transplant-associated thrombotic microangiopathy (TMA), among other conditions. Composite indices like the Endothelial Activation and Stress Index (EASIX) and its modified version (m-EASIX) may serve as accessible biomarkers for early identification. However, their utility in pediatric populations is unestablished. We aimed to explore whether EASIX and m-EASIX can help identify endothelial complications in this setting. Methods We conducted a prospective, single-center observational cohort study of 31 children and young adults undergoing HCT. Serial measurements of EASIX and m-EASIX scores, based on standard laboratory parameters, were collected at baseline and at multiple post-HCT time points (Days 0, 7, 14, 21, 28, and 100). Results Within 100 days after HCT, SOS and/or TMA developed in six patients. At Day 21, EASIX and m-EASIX scores were significantly higher in children with endothelial complications than in controls. The m-EASIX score also showed predictive value at Day 14. Receiver operating characteristic analysis showed discrimination at Day 21 for both scores (AUCs of 0.807 for EASIX and 0.865 for m-EASIX). Changes from baseline to Day 21 further improved accuracy, with thresholds achieving high sensitivity for screening patients at increased risk of SOS and/or TMA. The Day 21 landmark is most relevant for identifying patients at risk of later-onset or persistent endothelial injury, which remains clinically significant. Conclusions Our findings suggest that EASIX and m-EASIX may serve as practical and dynamic biomarkers for detecting endothelial injury in pediatric HCT recipients. The observation that Day 21 scores and their changes from baseline correlate with later complications highlights a potential window for risk stratification. However, these results should be interpreted cautiously, given the single-center design and limited sample size. Further research is needed to confirm whether these indices can reliably guide clinical decisions across diverse settings. Exploring their use in populations where reduced-intensity conditioning (RIC) and alternative donors are standard could provide important insights. Multicenter studies will be essential to validate these preliminary observations and refine biomarker-based strategies for post-HCT care.