Clinical Outcomes of Human Herpesvirus 6 Reactivation after Hematopoietic Stem Cell Transplantation

Abstract

Although human herpesvirus 6 (HHV-6) is known to reactivate during hematopoietic stem cell transplantation (HSCT), the clinical significance of this finding is controversial. We used a quantitative PCR test for HHV-6 to assay plasma samples prospectively collected from a cohort of 110 allogeneic HSCT recipients to evaluate the clinical effects of HHV-6 infection. A retrospective review of medical records was performed to determine clinical end points. HHV-6 reactivation occurred in 52 (47%) of the 110 subjects. Factors that increased the risk of subsequent HHV-6 reactivation were hematologic malignancy that occurred at a time other than the first remission (adjusted P = .002), a mismatch in the sexes of donor and recipient (adjusted P=.05), younger age (adjusted P = .01), and the receipt of glucocorticoids (adjusted P = .06). HHV-6 reactivation was associated with subsequent all-cause mortality (adjusted hazard ration [HR], 2.9; 95% confidence interval [CI], 1.1-7.5), grade 3-4 graft-versus-host disease (GVHD) (adjusted HR, 4.9; 95% CI, 1.5-16), a lower probability of monocyte engraftment (adjusted HR, 0.42; 95% CI; 0.22-0.80), a lower probability of platelet engraftment (adjusted HR, 0.47; 95% CI, 0.21-1.1; P = .05) and a higher platelet transfusion requirement (adjusted P = .02). A higher level of HHV-6 DNA was associated with subsequent central nervous system (CNS) dysfunction (HR, 21; 95% CI, 1.8-249). HHV-6 reactivation is common after allogeneic HSCT and is associated with subsequent delayed monocyte and platelet engraftment, increased platelet transfusion requirements, all-cause mortality, grade 3-4 GVHD, and CNS dysfunction.