100 Section - Prehabilitation, frailty syndrome and endothelial activation in adult candidates for allogeneic hematopoietic cell transplantation: A prospective cohort study

Frailty increases morbidity andmortalityin allo-HCT patients. Previous studies in older adults and individuals with cardiovascular risk have linked frailty to endothelial dysfunction, though this association remains unreported in allo-HCT. Given that endothelial activation occurs early post-allo-HCT due to conditioning, GVHD prophylaxis, alloreactivity, and complications, this study explores whether prehabilitation could modulate endothelial responses.

Design:

Between 2022-2025, all adult patients undergoing allo-HCT were categorized as fit, pre-frail or frail using the HCT Frailty Scale at admission (Salas et al., 2023). Since 2023, all patients underwent a structured exercise-based telematic prehabilitation. 

Endothelial activation was assessed using the Endothelial Activation and Stress Index (EASIX), at admission and days 0, +7, +14, +21, +28, +100, and +180 post-transplant. Biomarkers of endothelial activation and inflammation (VWF antigen, VCAM-1, thrombomodulin, REG3α, sTNFRI, ST2) were longitudinally quantified in plasma and sera samples.

Results:

Baseline characteristics and transplant procedures were similar across groups, except for a higher number of comorbidities in frail patients(p=0.023). 
EASIX trends showed a peak at day +21 in all frailty groups. Fit patients showed transient endothelial activation with progressive recovery. Pre-frail patients had sustained activation, while frail showed the highest and most prolonged elevations with limited recovery. Biomarkers followed a similar trend: frail patients had early VWF stabilization, late VCAM-1 increases, and progressive thrombomodulin elevation, suggesting persistent endothelial dysfunction.

Prehabilitated patients showed attenuated EASIX peaks and more favorable biomarker trajectories:  lower early VCAM-1 and TNFR1 elevations, stable thrombomodulin levels, higher late VWF concentrations and contained ST2 and REG3α-levels, suggesting enhanced endothelial regulation. 

Overall survival at 1-year was highest in pre-frail patients (87.3%), followed by fit (79.2%) and frail (62.5%; p=0.288).

Conclusion:

Frailty is associated with intensified and prolonged endothelial activation following allo-HCT, Telematic prehabilitation may mitigate these effects by enhancing endothelial and inflammatory regulation. These findings support incorporating prehabilitation and frailty assessment could reduce patient vulnerability.