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HHV-6 reactivation linked to central nervous system dysfunction after HCT
Zerr DM. Blood. 2011;117:5243-5249.
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Human herpesvirus-6 reactivation in hematopoietic cell transplantation recipients strongly predicted central nervous system dysfunction, according to results from a recent study.
“These data provide supporting evidence that [human herpesvirus-6] has a direct effect on the [central nervous system] and that [human herpesvirus-6] DNA detection in the blood after [hematopoietic cell transplantation] is clinically meaningful,” Danielle M. Zerr, MD, MPH, medical director of infection prevention at Seattle Children’s Hospital and affiliate investigator at the Fred Hutchinson Cancer Research Center, and colleagues wrote in Blood.
Although previous small studies and case reports have documented poor outcomes among hematopoietic cell transplantation (HCT) recipients with human herpesvirus-6 (HHV-6), such as impaired neurocognitive function 80 days after transplant and decreased quality of life 1 year after transplantation, the effects of the virus on the central nervous system are still incompletely understood. To further assess these relationships, the researchers enrolled 474 patients before allogeneic HCT evaluation in a large, prospective, randomized clinical trial.
A total of 315 patients were eligible for transplant and were included in the final analysis. Among these patients, 111 had HHV-6 detected in the 84 days after transplant. Median onset of HHV-6 reactivation was 20 days after transplant, with an average 4-day duration.
The researchers determined that patients with HHV-6 were more likely to develop delirium (adjusted OR=2.5; 95% CI, 1.2-5.3) and neurocognitive decline (adjusted OR=2.6; 95% CI, 1.1-6.2) after the procedure compared with other recipients, even after controlling for known risk factors.
Among the 89 patients who had positive delirium assessments, median onset to delirium episode was 15 days after transplant, with a median duration of 6 days. “We also found a stronger effect of HHV-6 on delirium in patients with more advanced underlying disease,” the researchers wrote.
A multivariate analyses of the 101 patients with HHV-6 who completed neurocognitive assessments revealed that clinically significant neurological declines occurred most commonly among patients who experienced reactivation in domains involving executive functioning, particularly attention/processing speed and concentration.
Findings were not clinically significant in domains involving memory and functions such as visuospatial perception and fine motor/speed/coordination.
Furthermore, data indicated that HHV-6 reactivation was associated with three conditions: the use of cord blood, the lessening of intensity conditioning, and the presence of unrelated transplants. HHV-6 antiviral therapy after transplant did not affect reactivation outcomes, but the researchers said few patients were administered this medication early after the procedure.
“These findings highlight the potential importance of targeting cord blood transplant recipients or patients with more advanced underlying disease for an antiviral intervention study,” the researchers wrote.
Cerebrospinal fluid testing and brain imaging were not available for all patients with HHV-6 associated delirium, and thus the proportion of patients with HHV-6 encephalitis was unable to be determined, they said, adding that incomplete neurocognitive testing was another limitation.
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