Human Herpesvirus 6 Reactivation, Delirium, and the Effect of Antiviral Prophylaxis Strategies After Cord Blood Transplantation
Background: Human herpesvirus 6 (HHV-6) reactivates in the majority of cord blood transplantation (CBT) recipients and is associated with significant morbidity. We previously reported that HHV-6 reactivation after hematopoietic cell transplantation (HCT) is associated with delirium (Zerr et. al. 2011, Blood 117: 5243), but only 21 patients (7%) of the cohort received CBT. Here we examine whether HHV-6 reactivation increases the risk for delirium after CBT and if intensive antiviral prophylaxis can reduce its impact.
Methods: We tested for HHV-6 by twice weekly plasma PCR until day +84 in a prospective cohort of 44 CBT recipients, 34 of whom were assessed for delirium 3 times weekly. Twenty patients were included in our original study (one patient receiving foscarnet was excluded). Antiviral prophylaxis strategies in CMV seropositive patients changed during enrollment from standard prophylaxis (acylcovir 800 mg twice daily) to intensive prophylaxis (ganciclovir 5 mg/kg daily on days -8 to -2 and acyclovir 800 mg three times daily on days 0 to +100) (Milano et. al. 2011, Blood 118: 5689). Delirium was modeled using longitudinal logistic regression with generalized estimating equations, and Cox proportional hazards were used to evaluate risk factors for HHV-6 reactivation.
Results: HHV-6 was detected in 66% of the cohort, and 27% of assessed patients had delirium. Patients with high-level viremia (>1000 copies/ml, 48%) were more likely to develop delirium (odds ratio [OR], 3.05; 95% confidence interval [CI], 1.03-9; p=0.043). This relationship was maintained in a series of bivariate models except when adjusting for comorbidity, which was a stronger predictor of delirium. Comorbidity score was not associated with HHV-6 reactivation. Intensive prophylaxis was given to 39% of patients and appeared to reduce risk of high-level viremia (adjusted hazard ratio, 0.28; 95% CI, 0.1-0.76; p=0.013) (Fig. 1). We were unable to analyze the effect of intensive prophylaxis on delirium due to sample size.
HHV-6 reactivation with high-level
viremia after CBT is independently associated with delirium. An intensive
antiviral prophylaxis strategy mitigated HHV-6 reactivation, but larger studies
are needed to assess this association with outcomes.
Genentech/Roche: Consultant, Research support
Gilead: Consultant, Research support
Clinigen: Consultant, Research support
W. Leisenring, None
H. Xie, None
C. Delaney, None
A. Adler, None
D. Zerr, Sage Products: Investigator, Research support
Chimerix, Inc.: Investigator, Research support