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. 2012 Nov;18(11):1700-8.
doi: 10.1016/j.bbmt.2012.05.012. Epub 2012 May 26.

HHV-6 reactivation and associated sequelae after hematopoietic cell transplantation

Danielle M Zerr  1 , Michael Boeckh, Colleen Delaney, Paul J Martin, Hu Xie, Amanda L Adler, Meei-Li Huang, Lawrence Corey, Wendy M Leisenring
Affiliations

HHV-6 reactivation and associated sequelae after hematopoietic cell transplantation

Danielle M Zerr et al. Biol Blood Marrow Transplant. 2012 Nov.

Abstract

Human herpesvirus 6 (HHV-6) reactivation has been associated with acute graft-versus-host-disease (aGVHD), cytomegalovirus reactivation, and mortality after allogeneic hematopoietic cell transplantation (HCT), but previous studies have yielded inconsistent results. We performed a large prospective study of allogeneic HCT recipients in order to more definitively define the relationships between HHV-6 and these important outcomes. Plasma specimens were collected prospectively from 315 allogeneic HCT recipients and tested for HHV-6 DNA at baseline and twice weekly for 12 weeks. Cox proportional hazards models were used to evaluate the time-dependent associations between HHV-6 reactivation and the targeted outcomes. HHV-6 was detected in 111 of 315 patients (35%) at a median of 20 days after HCT. HHV-6 reactivation was associated with subsequent cytomegalovirus reactivation (adjusted hazard ratio [aHR], 1.9; 95% confidence interval [CI], 1.3-2.8; P = .002). High-level HHV-6 (>1,000 HHV-6 DNA copies/mL) was associated with subsequent grades II to IV aGVHD (aHR, 2.4; 95% CI, 1.60-3.6; P < .001). High-level HHV-6 reactivation was also associated with nonrelapse mortality (aHR, 2.7; 95% CI, 1.2-6.3; P = .02). HHV-6 reactivation was independently and quantitatively associated with increased risk of subsequent cytomegalovirus reactivation, aGVHD, and mortality after HCT. A randomized antiviral trial is warranted to establish causality between HHV-6 and these endpoints and to determine if reducing HHV-6 reactivation will improve outcome after HCT.

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Figures

Figure 1
Figure 1
Consort diagram
Figure 2
Figure 2
Results from multivariable models evaluating HHV-6 reactivation as a risk factor for subsequent aGVHD by day 100. A. Full cohort. B. Excluding Cord Blood recipients. Covariates included in the final multivariable models: 1age, 2conditioning regimen, 3stem cell source, 4sex, 5underlying disease, 6HLA match, 7CMV serostatus, 8CD34 dose, 9co-morbidity index, 10female donor/male recipient.
Figure 2
Figure 2
Results from multivariable models evaluating HHV-6 reactivation as a risk factor for subsequent aGVHD by day 100. A. Full cohort. B. Excluding Cord Blood recipients. Covariates included in the final multivariable models: 1age, 2conditioning regimen, 3stem cell source, 4sex, 5underlying disease, 6HLA match, 7CMV serostatus, 8CD34 dose, 9co-morbidity index, 10female donor/male recipient.
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References

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