139. HHV-6 Reactivation and Associated Sequelae following Hematopoietic Cell Transplantation
Session: Oral Abstract Session: Clinical Virology and Treatment
Friday, October 21, 2011: 9:00 AM
Room: 156ABC
Background: Human herpesvirus 6 (HHV-6) reactivation frequently occurs following hematopoietic cell transplantation (HCT) and has been variably associated with acute graft versus host disease (aGVHD), cytomegalovirus (CMV) reactivation, and mortality. We investigated the potential associations between HHV-6 and these outcomes.

Methods: Allogeneic HCT recipients were prospectively tested for HHV-6 at baseline and twice-weekly for 12 weeks post-HCT using plasma PCR. Subjects were tested weekly for CMV reactivation. One person blinded to HHV-6 status assessed subjects for aGVHD. Non-relapse mortality was evaluated at day 200 post-HCT.  Multivariable Cox proportional hazards models were used to evaluate the time-dependent associations between HHV-6 and these outcomes.

Results: HHV-6 was detected in 111 (35%) of the 315 patients a median of 20 days post-HCT. HHV-6 reactivation was independently associated with subsequent CMV reactivation (adjusted hazard ratio (aHR) 1.8, 95% confidence interval (CI) 1.3-2.7, p=0.002).  HHV-6 was also independently associated with subsequent grades 2-4 overall aGVHD (aHR 1.4, 95% CI 1.01-1.9, p=0.04) and this relationship strengthened when evaluating high-level (>1,000 DNA copies/mL) HHV-6 reactivation (aHR 2.4, 95% CI 1.6-3.6, p < 0.001).  HHV-6 was evaluated as a risk factor for organ-specific sub-types of aGVHD: skin, gastrointestinal, and liver. The strongest relationship was observed between HHV-6 and skin aGVHD, where HHV-6 was an independent predictor of stages 2-4 skin aGVHD (aHR 1.6, 95% CI 1.01-2.4, p=0.04) and high-level HHV-6 reactivation was an independent predictor of both stages 2-4 and 3-4 skin aGVHD (aHR 1.9, 95% CI 1.1-3.3, p=0.02 and aHR 2.0, 95% CI 1.1-3.8, p=0.03, respectively). High-level HHV-6 reactivation was independently associated with non-relapse mortality (aHR 2.7, 95% CI 1.2-6.3, p=0.02). This association diminished when grades 3-4 overall aGVHD, but not when grades 2-4 aGVHD, was added to the model.

Conclusion: HHV-6 was associated with CMV reactivation, aGVHD, and mortality following HCT.  Acute GVHD may be in the causal pathway of the association between HHV-6 and mortality.  An antiviral intervention trial in HCT recipients will clarify the role HHV-6 plays in these outcomes.

Subject Category: O. Transplant infectious diseases

Danielle Zerr, MD, MPH1,2, Michael Boeckh, MD, FIDSA2,3, Colleen Delaney, MD, MSc2,3, Paul Martin, MD2,3, Hu Xie, MSc3, Amanda Adler, BA1, Meei-Li Huang, PhD3, Larwrence Corey, MD2,3 and Wendy Leisenring, ScD3, (1)Seattle Children's Hospital Research Institute, Seattle, WA, (2)University of Washington, Seattle, WA, (3)Fred Hutchinson Cancer Research Center, Seattle, WA


D. Zerr, Sage products, Inc.: Grant Investigator, Research grant
Vioguard, Ltd.: Grant Investigator, Research grant
NIH/NIAID: Grant Investigator, Research grant

M. Boeckh, Roche/Genentech: Consultant and Grant Investigator, Consulting fee and Research grant
Chimerix, Inc: Consultant and Grant Investigator, Consulting fee and Research support

C. Delaney, None

P. Martin, None

H. Xie, None

A. Adler, None

M. L. Huang, None

L. Corey, None

W. Leisenring, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.