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 Blood, 15 October 2007, Vol. 110, No. 8, pp. 3071-3077.
Prepublished online as a Blood First Edition Paper on May 21, 2007; DOI 10.1182/blood-2007-03-077644.

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TRANSPLANTATION

One-year acyclovir prophylaxis for preventing varicella-zoster virus disease after hematopoietic cell transplantation: no evidence of rebound varicella-zoster virus disease after drug discontinuation

Veronique Erard1, Katherine A. Guthrie1, Cara Varley1, Judson Heugel1, Anna Wald1,3, Mary E. D. Flowers1,3, Lawrence Corey1,3,4, and Michael Boeckh1,3

1 Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; 2 Department of Epidemiology 3 Department of Medicine, and 4 Department of Laboratory Medicine, University of Washington, Seattle

No consensus exists on whether acyclovir prophylaxis should be given for varicella-zoster virus (VZV) prophylaxis after hematopoietic cell transplantation because of 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 1 year is beneficial, we examined 3 sequential cohorts receiving acyclovir from day of transplantation until engraftment for prevention of herpes simplex virus reactivation (n = 932); acyclovir or valacyclovir 1 year (n = 1117); or acyclovir/valacyclovir for at least 1 year or longer if patients remained on immunosuppressive drugs (n = 586). In multivariable statistical models, prophylaxis given for 1 year significantly reduced VZV disease (P < .001) without evidence of rebound VZV disease. Continuation of prophylaxis beyond 1 year in allogeneic recipients who remained on immunosuppressive drugs led to a further reduction in VZV disease (P = .01) but VZV disease developed in 6.1% during the second year while receiving this strategy. In conclusion, acyclovir/valacyclovir prophylaxis given for 1 year led to a persistent benefit after drug discontinuation and no evidence of a rebound effect. To effectively prevent VZV disease in long-term hematopoietic cell transplantation survivors, additional approaches such as vaccination will probably be required.


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