Here are some of the key findings on the role of HHV-6 in GVHD:

  • Aoki and colleagues studied 236 patients who underwent allo-SCT and found that HHV-6 reactivation was associated with a higher incidence of of GVHD (HR =1.87) had significantly higher non-relapse mortality (27.7% versus 13.7%), as well as worse overall survival (42.1% versus 59.0%) compared to those who did not develop HHV-6 reactivation (Aoki 2015).
  • A recent study of 106 children who underwent SCT found that progression to grades II-IV GVHD was associated with HHV-6 reactivation in 9/10 (90%). Furthermore, HHV-6 was the only infection that demonstrated this association (Verhoeven 2015).
  • In a study that analyzed 13 DNA viruses in 105 allo-SCT patients, HHV-6 was the only virus tied to the onset of aGVHD. The study also revealed that patients treated with steroids were at a significantly greater risk of developing HHV-6 reactivation, and that deactivation was associated with a more severe skin but not liver or gut aGVHD (Inazawa 2015).
  • A study 235 allogeneic stem cell transplant patients found HHV-6 reactivation to be strongly associated with delayed platelet engraftment, early post-transplantation mortality, and the development of aGVHD (Dulery 2012).
  • A study of 315 allo-SCT recipients by Zerr and colleagues revealed a significant association between high-level (≥1000 copies/mL plasma) HHV-6 reactivation and grades III–IV aGVHDwith overall survival and non-relapse mortality (Zerr 2012).
  • A study of 49 HSCT patients found that patients with a viral load ≥87 copies/mL on day 30 post-HSCT developed grades II–IV aGVHD within 100 days, suggesting that HHV-6 reactivation is a high risk factor for aGVHD (Gotoh 2014).
  • In a study of 365 patients undergoing HSCT, HHV-6 reactivation was a predictive factor for acute GVHD (HR 1.66) and GVHD was a predictive factor for HHV-6 reactivation (Pichereau 2012).
  • Appleton and colleagues who compared skin and rectal biopsies from 34 allogeneic bone marrow transplant recipients and 23 autologous recipients.  In allogeneic recipients who developed severe GVHD, HHV-6 DNA was detected in 92% of skin and/or rectal compared to 55% and 22% of biopsies from allogeneic recipients with moderate and mild GVHD, respectively, suggesting an association between HHV-6 DNA and GVHD severity (Appleton 1995).

Key Papers: HHV-6 and Graft-versus-Host Disease

Aoki 2015 Impact of Human Herpesvirus-6 Reactivation on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation
Verhoeven 2015 Reactivation of Human Herpes Virus-6 after Pediatric Stem Cell Transplantation: Risk Factors, Onset, Clinical Symptoms and Association with Severity of Acute Graft-Versus-Host Disease
Inazawa 2015 Large-scale multiplex polymerase chain reaction assay for diagnosis of viral reactivations after allogeneic hematopoietic stem cell transplantation.
Gotoh 2014 Human herpesvirus 6 reactivation on the 30th day after allogeneic hematopoietic stem cell transplantation can predict grade 2–4 acute graft-versus-host disease
De Pagter 2013 Human herpes virus 6 reactivation: important predictor for poor outcome after myeloablative, but not non-myeloablative allo-SCT
Dulery 2012 Early Human Herpesvirus Type 6 Reactivation after Allogeneic Stem Cell Transplantation: A Large-Scale Clinical Study
Zerr 2012 HHV-6 Reactivation and Associated Sequelae after Hematopoietic Cell Transplantation
De Pagter 2008 Human Herpes Virus 6 Plasma DNA Positivity after Hematopoietic Stem Cell Transplantation in Children: an Important Risk Factor for Clinical Outcome
Wang 2008 Correlations of human herpesvirus 6B and CMV infection with acute GVHD in recipients of allogeneic haematopoietic stem cell transplantations
Zerr 2005 Clinical Outcomes of Human Herpesvirus 6 Reactivation after Hematopoietic Stem Cell Research
Takemoto 2000 Evaluation of CMV/human herpes virus-6 positivity in bronchoalveolar lavage fluids as early detection of acute GVHD following BMT: evidence of a significant relationship
Wang 1999 Human herpesvirus 6 infection inhibits specific lymphocyte proliferation responses and is related to lymphocytopenia after allogeneic stem cell transplantation