High incidence of hematologic malignancy relapse after allogeneic transplantation in patients with low Epstein-Barr virus-specific T-cell counts

Abstract

Background: Association between low counts of herpesvirus-specific T cells and subsequent relapse of hematologic malignancy has been shown in two retrospective studies.

Methods: Here we present results of a prospective validation study. Multiple subsets of Epstein-Barr virus (EBV)-specific T cells were measured in 69 patients on day 56 and 84, using intracellular flow cytometry after incubation of blood mononuclear cells (MNCs) with EBV peptides or lysate.

Results: All EBV T-cell subsets measured, both on day 56 and 84, were lower in patients who did versus did not subsequently relapse. This was most significant for day 56 EBV lysate-stimulated CD8 T cells producing interferon-gamma. Patients with day 56 counts of this subset >5/µL had a significantly lower likelihood of relapse compared with those with ≤5/µL (subhazard ratio, 5.7; P = 0.007). Similar significant associations were shown for a total of seven EBV T-cell subsets on day 56 and nine subsets on day 84. However, sensitivity and specificity of relapse prediction using the count of any subset was low (area under the curve of receiver-operator characteristic curve was <0.8).

Discussion: In conclusion, the association between EBV T-cell counts and subsequent relapse is valid. However, its clinical utility appears to be limited.

Keywords: Epstein-Barr virus; allogenic hematopoietic cell transplantation; relapse.