Submitted March 2, 2007
Accepted May 17, 2007
One-year acyclovir prophylaxis for preventing varicella-zoster virus (VZV) disease following hematopoietic cell transplantation: no evidence of rebound VZV disease after drug discontinuation
Veronique Erard, Katherine A Guthrie, Cara Varley, Judson Heugel, Anna Wald, Mary E.D. Flowers, Lawrence Corey, and Michael Boeckh*
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
Dept of Epidemiology, University of Washington, Seattle, WA, United States
Dept of Medicine, University of Washington, Seattle, WA, United States
Dept of Laboratory Medicine, University of Washington, Seattle, WA, United States
* Corresponding author; email: mboeckh{at}fhcrc.org.
No consensus exists on whether acyclovir prophylaxis should be given for VZV prophylaxis after hematopoietic cell transplantation (HCT) due to the concern of 'rebound' VZV disease after discontinuation of prophylaxis. To determine whether rebound VZV disease is an important clinical problem and whether prolonging prophylaxis beyond one year is beneficial we examined 3 sequential cohorts receiving acyclovir from day of transplantation until engraftment for prevention of HSV reactivation (N=932); acyclovir or valacyclovir one year (N=1117); or acyclovir/valacyclovir for at least one year or longer if patients remained on immunosuppressive drugs (N= 586). In multivariable statistical models, prophylaxis given for one year significantly reduced VZV disease (p< 0.001) without evidence of rebound VZV disease. Continuation of prophylaxis beyond one year in allogeneic recipients who remained on immunosuppressive drugs led to a further reduction in VZV disease (p=0.01) but 6.1% developed VZV disease during the second year while receiving this strategy. In conclusion, acyclovir/valacyclovir prophylaxis given for one year led to a persistent benefit after drug discontinuation and no evidence of a rebound effect. To effectively prevent VZV disease in long-term HCT survivors, additional approaches such as vaccination will likely be required.
