Von Willebrand factor as a potential predictive biomarker of early complications of endothelial origin after allogeneic hematopoietic cell transplantation.

Abstract Transplant-associated endothelial complication (TA-EC) are life-threatening complications after allogeneic hematopoietic cell transplantation (alloHCT) and include thrombotic microangiopathy, systemic and pulmonary syndromes. There is no validated biomarker to predict them. We conducted a retrospective study to assess the role of von Willebrand factor (VWF) as a predictive biomarker of TA-EC on 127 adult alloHCT recipients. 28 patients (22%) had at least one endothelial-related complication within a four-week window after alloHCT. All conditioning regimens induced both synthesis and activation of VWF. VWF:RCo ≥200% on day -4 of alloHCT was associated with TA-EC, and sepsis, as well as elevated EASIX score and CRP levels in univariate analyses. Multivariate analyses showed that only VWF:RCo retained an independent impact. VWF:RCo, EASIX and CRP constituted risk factors for survival and non-relapse mortality in univariate analyses, even in patients not developing TA-EC. Multivariate analyses confirmed the impact of the biomarkers. RNA sequencing data from 113 patients from the BEAT AML cohort who underwent alloHCT confirmed the prognostic impact of VWF gene expression. Our findings show that conditioning regimens increase VWF:Ag and VWF:RCo in alloHCT. Moreover, VWF:Rco ≥200% on day -4 appears to be a biomarker of endothelial vulnerability and a risk factor for endothelial-related complications and overal survival.