EASIX-1 year and late mortality after allogeneic stem cell transplantation.

Patients with haematological malignancies who survive the first year after allogeneic stem cell transplantation (alloSCT) without relapse have a substantial risk of non-relapse mortality (NRM), and predictive markers are missing. The Endothelial Activation and Stress Index (EASIX) predicts endothelial complications and NRM early after alloSCT. We hypothesised that EASIX assessed 1 year after alloSCT in disease-free survivors may predict late NRM. Relapse-free survivors at one year after alloSCT were retrospectively studied in two independent cohorts (training cohort: n=610, merged validation cohort: n=852). EASIX determined one year after alloSCT was correlated with overall survival (OS), NRM, and relapse. Serum endothelial and inflammatory markers were measured in the training cohort and correlated with EASIX-1y. EASIX-1year predicted OS and NRM but not relapse risk in both, training and validation cohort in univariable and multivariable Cox regression analyses. Brier score and c-index analyses validated the univariable EASIX effects. There was no significant interaction between EASIX-1year and incidence of chronic GvHD on OS. EASIX-1year predicted outcome irrespective of pre-existing comorbidities. Principal causes of NRM in both, training and validation cohorts were infections with and without GvHD, as well as cardiovascular complications. EASIX-1y correlated with sCD141 and interleukin-18, but not with C-reactive protein, suppressor of tumorigenicity (ST)-2, angiopoietin-2, CXCL9 or CXCL8. EASIX-1year is the first validated predictor of late overall and non-relapse mortality. High-risk patients as defined by EASIX-1year might be considered for intensified surveillance and prophylactic measures.