Easix Score Correlates With Endothelial Dysfunction Biomarkers and Predicts Risk of Acute Graft-Versus-Host Disease After Allogeneic Transplantation
Pedraza, Alexandra (Hospital Clínic i Provincial de Barcelona)
Salas, María Queralt (Hospital Clínic i Provincial de Barcelona)
Rodríguez-Lobato, Luis Gerardo (Hospital Clínic i Provincial de Barcelona)
Escribano Serrat, Silvia (Hospital Clínic i Provincial de Barcelona)
Suárez-Lledó Grande, María (Hospital Clínic i Provincial de Barcelona)
Martínez Cibrián, Núria (Hospital Clínic i Provincial de Barcelona)
Solano, María Teresa (Hospital Clínic i Provincial de Barcelona)
Arcarons, Jordi (Hospital Clínic i Provincial de Barcelona)
Rosiñol, Laura (Hospital Clínic i Provincial de Barcelona)
Gutiérrez-García, Gonzalo (Hospital Clínic i Provincial de Barcelona)
Fernandez Aviles, Francesc (Hospital Clínic i Provincial de Barcelona)
Moreno-Castaño, Ana Belén (Hospital Clínic i Provincial de Barcelona)
Molina, Patricia (Hospital Clínic i Provincial de Barcelona)
Pino, Marc (Hospital Clínic i Provincial de Barcelona)
Carreras, E. (Fundació i Institut de Recerca Josep Carreras contra la Leucèmia (Campus Clínic))
Diaz-Ricart, Maribel (Hospital Clínic i Provincial de Barcelona)
Rovira, Montserrat (Hospital Clínic i Provincial de Barcelona)
Palomo, Marta (Hospital Clínic i Provincial de Barcelona)
Martínez, Carmen (Hospital Clínic i Provincial de Barcelona)
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	Plasma biomarkers of endothelial dysfunction have been postulated for the diagnosis and prognosis of acute graft-versus-host disease (aGVHD). However, their use is not validated in clinical practice yet. The endothelial activation and stress index (EASIX), a simple score based on routine laboratory parameters, is considered to be an indirect marker of endothelial damage. High value of EASIX was correlated with worse non-relapse mortality (NRM) and overall survival (OS) and a high risk of sinusoidal obstructive syndrome and transplant-associated thrombotic microangiopathy (TA-TMA). This study investigates the predictive value of plasma biomarkers and the EASIX score for the prediction of aGVHD. We assessed vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor receptor 1 (TNFR1), and VWF:Ag plasma levels and the EASIX score before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and on days 0, 3, 7, 14, and 21 in an experimental cohort (n = 33). EASIX was transformed to a base-2 logarithm to perform the analysis. For the most relevant biomarkers, we estimate the optimal cutoff values and the discriminatory ability to differentiate patients with high-risk of aGVHD. The conclusions obtained in the experimental cohort were validated in a large cohort of 321 patients at the same institution. Plasma biomarkers and EASIX showed similar post-transplantation dynamics consisting of a progressive increase. Multivariate analysis showed an association between high TNFR1 levels and Log-2 EASIX score on day 7 after transplantation with an increased likelihood of developing aGVHD (hazard ratio [HR] = 1, P =. 002; HR = 2. 31, P =. 013, respectively). Patients with TNFR1 ≥1300 ng/mL (HR = 7. 19, P =. 006) and Log2-EASIX ≥3 (HR = 14. 7, P <. 001) at day 7 after transplantation were more likely to develop aGVHD with high predictive accuracy (C-index of 74% and 81%, respectively). In the validation cohort, patients with Log2-EASIX ≥3 on day 7 after transplantation presented a significantly higher incidence of grade II-IV aGVHD (HR = 1. 94, P =. 004) independent of GVHD prophylaxis (HR = 0. 38, P =. 004), conditioning regimen (HR = 0. 59, P =. 02) and type of donor (HR = 2. 38, P =. 014). Differential degree of endothelial damage can be measured using both EASIX score and plasma biomarkers in the early post-transplantation period. Patients at risk of developing aGVHD could be easily identified by a high EASIX score. Both indicators of endothelial activation represent a promising approach to predict aGVHD.
Grants:	Instituto de Salud Carlos III PI19/00888
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Acute GVHD ; Allogeneic hematopoietic stem cell transplantation ; Biomarkers ; EASIX ; Endothelial dysfunction ; Graft-versus-host disease
Published in:	Transplantation and cellular therapy, Vol. 30 Núm. 2 (february 2024) , p. 187.e1-187.e12, ISSN 2666-6367

DOI: 10.1016/j.jtct.2023.11.016
PMID: 38000709

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