High levels of circulating extracellular vesicles (EV), including total circulating EV (TEV) and erythrocyte-derived EVs (EryEV), were associated with greater rates of acute graft vs host disease (aGVHD) among patients who underwent an allogeneic stem cell transplant (allo-SCT) to treat a hematologic malignancy, according to the results of study published in the journal Experimental Hematology.

There is an unmet need for improved identification of GVHD and its treatment. EVs can serve as biomarkers of cell damage, among other functions. The aim of this study was to determine if EVs could indicate or predict GVHD after allo-SCT.

In the study, blood was collected from 40 patients at neutrophil engraftment after allo-SCT for a hematologic malignancy. Circulating EV analysis was performed using flow cytometry. The median follow-up of the study was 75 months.

Continue Reading

The median age of the cohort was 52 and half of patients were in their first or second remission. The stem cell source was peripheral blood among 58% of patients, whereas 25% had stem cells from bone marrow and 17% from cord blood. The donor was unrelated among 45% of patients, haploidentical related among 30%, and matched related among 25%. Reduced-intensity condition was used for 73% of patients; of whom, 48% also received total body irradiation.

The GVHD prophylaxis included cyclosporine with mycophenolate mofetil (MMF) in 48% of patients, with MMF plus posttransplant cyclophosphamide in 30%, or with methotrexate in 22%. The overall incidence of grade II-IV aGVHD was 38% at 100 days.

The cumulative incidence of grade II-IV aGVHD was higher among patients with greater levels of TEV (>516 /μL), with a rate of 54% compared with 21% among patients with lower levels (P=.02). Similarly, 59% of patients with grade II-IV aGVHD had higher levels of EryEV counts (>357 /μL) compared with 26% of patients with lower counts (P =.04).

The association between aGVHD, TEV, and EryEV counts was stronger for patients who received reduced intensity conditioning prior to their allo-SCT. There were 77% and 22% of patients with aGVHD, who had higher versus lower TEV counts (P =.003), respectively, and 89% and 27% for those who had higher versus lower EryEv counts (P =.002). Overall, TEV and EryEV counts were higher among patients who received myeloablative conditioning.

Platelet-derived EV counts were not associated with the incidence of aGVHD. The authors concluded that “our data suggest that the measurement of cell-derived EV at engraftment can be used as a preemptive biomarker for aGVHD.”


Carneiro TX, Marrese DG, dos Santos MG, et al. Circulating extracellular vesicles as a predictive biomarker for acute graft-versus-host disease. Exp Hematol. Published online November 15, 2022. doi: 10.1016/j.exphem.2022.11.004