Early Human Herpesvirus Type 6 Reactivation after Allogeneic Stem Cell Transplantation: A Large-Scale Clinical Study

Abstract

This study investigated the impact of human herpesvirus type 6 (HHV6) reactivation within 100 days of allogeneic stem cell transplantation (allo-SCT) on patient outcomes. HHV6 plasma loads were monitored weekly by quantitative PCR. Of 235 consecutive patients, 112 (48%) had an early positive HHV6 PCR test (group A) and 123 (52%) did not (group B). HHV6 reactivation was less frequent in patients who received reduced-intensity conditioning (P = .028). In group A, only 6 patients (5%) were asymptomatic; the most common clinical manifestations were fever (n = 60), skin rash (n = 57), diarrhea (n = 51), pulmonary complications (n = 19), and neurologic disorders (n = 12). Compared with the patients in group B, those in group A experienced delayed platelet engraftment (P = .003) and more frequent grade II-IV acute graft-versus-host disease (GVHD) (47% versus 30% in group B; P = .009). In multivariate analysis, the most important factors influencing the development of grade II-IV acute GVHD development were early HHV6 reactivation (P = .03) and unrelated donor status (P < .001). HHV6 reactivation adversely influenced 6-month survival (P = .04). Of the 38 evaluable patients receiving antiviral treatment, 34 had a significantly decreased HHV6 load. Our findings indicate that HHV6 reactivation after allo-SCT is associated with delayed platelet engraftment, early posttransplantation mortality, and the development of acute GVHD. Careful monitoring of HHV6 by PCR is warranted during the early posttransplantation period.

Human herpes virus 6 reactivation: important predictor for poor outcome after myeloablative, but not non-myeloablative allo-SCT

“…HHV6 reactivation occurred early and before the occurrence of aGVHD, and thus before the initiation of immunosuppressive treatment, whereas the majority of EBV and HCMV reactivations (63%) occurred during aGVHD treatment (median interval for GVHD and EBV/HCMV reactivation 9 days, range 0-38, data not shown). Very recently, Dulery et al 6 confirmed these data and observed frequent HHV6 reactivation after MA conditioning prior to aGVHD treatment.…”

“…4 Very recently, Dulery et al 6 showed high incidence of HHV6 reactivation in adults after (MA) HSCT (48%). Others noted higher incidences of HHV6 reactivation: Zerr et al 7 performed a prospective study among 110 adult patients treated with HSCT, in which 47% of the patients had a HHV6 reactivation, 5 and Hentrich et al 25 found that 42% of 228 patients showed HHV6 reactivation.…”

“…[1][2][3] Human herpes virus 6 (HHV6), which reactivates early after HSCT, was found to be associated with aGVHD and increased NRM in children and, recently, in adults. [4][5][6][7] Predictors for the development of HHV6 reactivation are largely unknown. To date, only broad-spectrum and relatively toxic antiherpes virus drugs (for example, (val)ganciclovir and foscarnet-sodium) are used in the treatment of HHV6 disease or -reactivation.…”

HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis

“…Some publications have suggested that the increased prevalence of HHV-6 reactivation may be due to the large number of immature ('antigen-naive') T cells present in umbilical CB, which inherently lacks the mature ('antigenexperienced' or 'memory') T cells necessary for immune reconstitution following HSCT. [35][36][37] In addition, because the newborn is generally naive for HHV-6 infection, CB lacks HHV-6-specific T cells, which could help in the containment of HHV-6 replication following engraftment. In fact, CB-derived T lymphocytes are often utilized to facilitate the active replication of HHV-6 in vitro.…”

Pleurisy as a novel clinical manifestation associated with human herpesvirus 6 after unrelated cord blood transplantation

“…4,5 To date, however, HHV6-associated pleurisy has not been recognized as a complication of HSCT. In this report, we describe an adult HSCT recipient who developed HHV6-associated pleurisy after an unrelated cord blood transplantation (CBT).…”