Five Year Cumulative Incidence of Herpes Zoster (HZ) in Autologous Hematopoietic Cell Transplant (HCT) Recipients who Received Long-Term Acyclovir or Valacyclovir Prophylaxis
Background: Antiviral prophylaxis with acyclovir/valacyclovir (ACV/VCV) after allogeneic HCT reduces HZ and its complications, but benefits of prophylaxis after autologous HCT are not well described. We determined the incidence of and risk factors for HZ over 5 years in a large cohort of autologous HCT recipients from an era that included ACV/VCV prophylaxis and maintenance chemotherapy for the underlying disease.
Methods: We retrospectively identified 1000 consecutive varicella zoster virus seropositive autologous HCT recipients from 2002 to 2010. Antiviral prophylaxis was prescribed with ACV 800 mg or VCV 500 mg twice daily for 1 year post-HCT. Cumulative incidence of HZ was evaluated and multivariable Cox regression models were used to evaluate adjusted hazard ratios (aHR) and associated confidence intervals (CI) for the association of ACV/VCV with HZ while adjusted for sex, type of transplant (single vs. tandem) and pre-HCT HZ.
Results: Patients were followed for a median of 39.7 months (interquartile range [IQR], 20.7-66.1 months). A total of 192 patients developed at least one HZ episode over 5 years following HCT with an overall cumulative incidence of 0.21 (95% CI, 0.18-0.24) (Figure 1) at a median of 19 months (IQR, 14.4-31.3 months). The majority of patients who developed HZ 157/192 (81.7%) were no longer taking prophylaxis at the time of HZ. A second episode of HZ occurred in 31/192 (16%) of patients at a median of 14.8 months (IQR, 7.1-24.9 months) after the first HZ episode (Figure 2). ACV/VCV had a protective effect against HZ (aHR, 0.61; 95% CI, 0.39-0.95; p=0.03). Disseminated disease occurred in 18/192 (9.4%) patients during the first HZ episode and 3/31 (9.7%) patients during the second episode of HZ after HCT.
Conclusion: In a large population of autologous HCT recipients who were prescribed one year of ACV/VCV, over 20% of patients developed HZ during 5 years of follow-up, with the majority occurring after completing antiviral prophylaxis. Improved prevention strategies (e.g. an effective vaccine) are needed to provide long-term protection against HZ in high-risk autologous HCT recipients.
Merck Research Laboratories: Investigator, Research support
W. Leisenring, None
S. Goyal, Merck Research Laboratories: Investigator, Research support
J. Yi, None
L. Kimball, None
I. Lee, Merck Research Laboratories: Employee and Shareholder, Salary
J. Hill, None
S. Seo, None
C. Davis, None
S. Pergam, Merck Research Laboratories: Consultant and Research Contractor, Consulting fee and Research support
K. L. Liaw, Merck Research Laboratories: Employee and Shareholder, Salary
L. Holmberg, None
M. Boeckh, Merck Research Laboratories: Consultant and Research Contractor, Consulting fee and Research support
GSK: Consultant and Research Contractor, Consulting fee and Research support