Easix Score Correlates With Endothelial Dysfunction Biomarkers and Predicts Risk of Acute Graft-Versus-Host Disease After Allogeneic Transplantation.

Autor: Pedraza A; Blood Bank Department, Biomedical Diagnostic Center, Banc de Sang i Teixits, Hospital Clínic Barcelona, Spain. Electronic address: acpedraza@clinic.cat., Salas MQ; Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases Hospital Clínic de Barcelona, IDIBAPS, Josep Carreras Institute, Barcelona, Spain., Rodríguez-Lobato LG; Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases Hospital Clínic de Barcelona, IDIBAPS, Josep Carreras Institute, Barcelona, Spain., Escribano-Serrat S; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Biomedical Diagnostic Center, Hospital Clínic de Barcelona, Spain., Suárez-Lledo M; Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases Hospital Clínic de Barcelona, IDIBAPS, Josep Carreras Institute, Barcelona, Spain., Martínez-Cebrian N; Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases Hospital Clínic de Barcelona, IDIBAPS, Josep Carreras Institute, Barcelona, Spain., Solano MT; Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases Hospital Clínic de Barcelona, IDIBAPS, Josep Carreras Institute, Barcelona, Spain., Arcarons J; Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases Hospital Clínic de Barcelona, IDIBAPS, Josep Carreras Institute, Barcelona, Spain., Rosiñol L; Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases Hospital Clínic de Barcelona, IDIBAPS, Josep Carreras Institute, Barcelona, Spain., Gutiérrez-García G; Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases Hospital Clínic de Barcelona, IDIBAPS, Josep Carreras Institute, Barcelona, Spain., Fernández-Avilés F; Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases Hospital Clínic de Barcelona, IDIBAPS, Josep Carreras Institute, Barcelona, Spain., Moreno-Castaño AB; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Biomedical Diagnostic Center, Hospital Clínic de Barcelona, Spain., Molina P; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Biomedical Diagnostic Center, Hospital Clínic de Barcelona, Spain., Pino M; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Biomedical Diagnostic Center, Hospital Clínic de Barcelona, Spain., Carreras E; Fundació i Institut de Recerca Josep Carreras contra la Leucèmia (Campus Clínic), Barcelona., Díaz-Ricart M; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Biomedical Diagnostic Center, Hospital Clínic de Barcelona, Spain., Rovira M; Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases Hospital Clínic de Barcelona, IDIBAPS, Josep Carreras Institute, Barcelona, Spain; Fundació i Institut de Recerca Josep Carreras contra la Leucèmia (Campus Clínic), Barcelona., Palomo M; Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Biomedical Diagnostic Center, Hospital Clínic de Barcelona, Spain; Haematology External Quality Assessment Laboratory, Biomedical Diagnostic Center, Biochemistry and Molecular Genetics Department, Biomedical Diagnostic Center, Hospital Clínic Barcelona, Barcelona, Spain., Martínez C; Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases Hospital Clínic de Barcelona, IDIBAPS, Josep Carreras Institute, Barcelona, Spain; Fundació i Institut de Recerca Josep Carreras contra la Leucèmia (Campus Clínic), Barcelona.
Jazyk: angličtina
Zdroj: Transplantation and cellular therapy [Transplant Cell Ther] 2024 Feb; Vol. 30 (2), pp. 187.e1-187.e12. Date of Electronic Publication: 2023 Nov 23.
DOI: 10.1016/j.jtct.2023.11.016
Abstrakt: 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.
Competing Interests: Disclosure of conflicts of interest All authors declare no competing financial interests.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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