HHV-6 reactivation and associated sequelae after hematopoietic cell transplantation.
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.
Department of Pediatrics, University of Washington, Seattle, Washington 98115, USA. danielle.zerr@seattlechildrens.org
Danielle M
DM
Zerr
Michael
M
Boeckh
Colleen
C
Delaney
Paul J
PJ
Martin
Hu
H
Xie
Amanda L
AL
Adler
Meei-Li
ML
Huang
Lawrence
L
Corey
Wendy M
WM
Leisenring
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002648:Child; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D019349:Roseolovirus Infections / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000821:virology; D012720:Severity of Illness Index; D016019:Survival Analysis; D014184:Transplantation, Homologous; D019562:Viral Load; D014775:Virus Activation