Human herpesvirus 6 can be detected in cerebrospinal fluid without associated symptoms after allogeneic hematopoietic cell transplantation

Abstract

BackgroundHuman herpesvirus 6 (HHV-6) is an opportunistic pathogen after hematopoietic cell transplantation (HCT) that is associated with central nervous system (CNS) dysfunction. ObjectivesThe aim of this study was to determine the frequency and significance of HHV-6 DNA detection in cerebrospinal fluid (CSF) after HCT. Study designWe identified patients with HHV-6 DNA in CSF using quantitative PCR. Patients with neurologic symptoms and HHV-6 DNA in CSF without identification of an alternative etiology were categorized as having HHV-6 CNS dysfunction. ResultsAmong 3902 allogeneic HCT recipients from 1998 to 2012, 51 of 124 tested patients had HHV-6 DNA in CSF; 37 met criteria for HHV-6 CNS dysfunction and 14 (27%) did not. Patients with an alternative diagnosis had longer time to HHV-6 detection and lower viral load in CSF. Six patients without HHV-6 CNS dysfunction were not treated and had no morbidity attributable to HHV-6. Kaplan–Meier analysis demonstrated poor overall survival among all patients. Variables associated with higher all-cause mortality in a multivariable Cox model included alternative diagnosis (adjusted hazard ratio [aHR], 8.4; 95% CI, 1.7–40.9; P=0.009) and higher peak plasma viral load (log10 scale) (aHR, 1.4; 95% CI, 1.1–1.9; P=0.01). ConclusionWe identified a number of allogeneic HCT recipients with HHV-6 DNA in CSF who did not meet criteria for HHV-6 CNS dysfunction. All patients had poor survival. Whether CSF HHV-6 DNA detection in patients without associated CNS dysfunction independently contributes to mortality and warrants treatment is unclear; management of these patients warrants further investigation.