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

Abstract

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.

EASIX is an effective marker in predicting mortality of traumatic brain injury patients

“…Then, the prognostic value of the EASIX incorporating lactate dehydrogenase, serum creatinine and platelet was verified in many kinds of patients including lower risk myelodysplastic syndromes, multiple myeloma, COVID-19, diffuse large B-cell lymphoma, small cell lung cancer, sepsis, and critically ill patients with advanced liver disease [10][11][12][13][14][15]. Some studies showed the significant correlation between the EASIX and levels of endothelial activation markers including interleukin-18, chemokine-X-C-ligand 8, C-X-C motif chemokine ligand 9, insulin like-growth-factor-1, suppressor of tumorigenicity-2, angiopoietin-2, soluble thrombomodulin [8,9]. As the marker of endothelial injury, the EASIX is readily obtained in clinical practice with less costs to evaluate the risk of complication and prognosis.…”

“…The endothelial activation and stress index (EASIX) has recently been designed and verified to evaluate the severity of endothelial injury after allogeneic stem-cell transplantation [7]. Researchers found it was associated with levels of endothelial activation markers such as interleukin-18, chemokine-X-C-ligand 8, insulin like-growth-factor-1, suppressor of tumorigenicity-2 [8,9]. Furthermore, the EASIX has been confirmed related with mortality of various patients such as multiple myeloma, COVID-19, diffuse large B-cell lymphoma, small cell lung cancer, sepsis [10][11][12][13][14].…”

Plasma from patients undergoing allogeneic hematopoietic stem cell transplantation promotes NETOSIS in vitro and correlates with inflammatory parameters and clinical severity

“…In recent years, evidence has accumulated that endothelial dysfunction in the context of inflammation and cytokine dysregulation is one of the mechanisms described in aGVHD and contributes to severe complications after allo-HSCT ( 8 , 9 ). In preclinical models, vulnerability biomarkers and ongoing endothelial tissue injury markers appear to be a high-priority goal to reduce the risks of allo-HSCT ( 10 ).…”