Extracellular vesicle phenotypic patterns associated with CMV, EBV and HHV-6 reactivation after haploidentical transplantation with post-transplant cyclophosphamide.

Authors

Giuseppe Lia, Clara Di Vito, Stefania Bruno, Jacopo Mariotti, Alessia Melis, Michela Calvi, Luisa Giaccone, Armando Santoro, Stefania Bramanti, Luca Castagna, Andrea Evangelista, Domenico Mavilio, Benedetto Bruno

Published in

Frontiers in immunology. Volume 17. Pages 1937675. Epub Oct 05, 2026.

Abstract

Human cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6) remain important causes of morbidity after allogeneic hematopoietic cell transplantation (HCT), yet biomarkers predicting viral reactivation are lacking. Extracellular vesicles (EVs) have emerged as promising liquid-biopsy tools in inflammatory and infectious diseases.
In this exploratory biomarker discovery study, 32 consecutive recipients of haploidentical HCT with post-transplant cyclophosphamide were prospectively enrolled. EV surface marker profiles were assessed by flow cytometry before transplantation and at predefined time points during the first three months post-HCT. Associations between EV phenotypes and viral reactivation were evaluated using logistic regression and time-varying Cox models.
CMV, EBV, and HHV-6 reactivation occurred in 20, 11, and 17 patients, respectively. Multivariable analyses showed that different EV phenotypic patterns were associated with CMV, EBV, and HHV-6 reactivation. CMV reactivation was associated with increased EV expression of CD44, CD86, CD140a, and CD144. EBV reactivation correlated with reduced CD30-positive EV concentrations and increased KRT18 expression. HHV-6 reactivation was associated with altered CD26, CD86, CD120a, and CD144 EV profiles. These associations remained significant after adjustment for acute graft-versus-host disease and concomitant viral infections.
Collectively, these exploratory findings support further validation of circulating EV phenotypes as candidate biomarkers for predicting and monitoring viral reactivation after haploidentical HCT.

PMID:
42898153
Bibliographic data and abstract were imported from PubMed on 20 Oct 2026.

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