Impact of the duration of antiviral prophylaxis on rates of varicella-zoster virus reactivation disease in autologous hematopoietic cell transplantation recipients

Abstract

Varicella-zoster virus (VZV) reactivation is a relatively common cause of morbidity following autologous hematopoietic cell transplant (auto-HCT). The Centers for Disease Control in 2009 recommended extending VZV prophylaxis for 1 year post-transplantation. We retrospectively analyzed rates of VZV reactivation following auto-HCT at our transplant center prior to and after the implementation of extended antiviral prophylaxis in June 2008. The study population was divided into three different cohorts according to the length of VZV prophylaxis as following: (1) prophylaxis until neutrophil recovery to ≥500/μL (n = 77), (2) prophylaxis for 6 months (n = 12), or (3) 12 months (n = 40) post-auto-HCT. All patients received acyclovir 400 mg oral or intravenously twice daily or valacyclovir 500 mg oral daily. For patients in whom VZV reactivation occurred, data was collected on severity of infection, time of onset, treatment, and any associated complications. One hundred twenty-nine patients undergoing auto-HCT between January 1, 2004 and January 31, 2010 were included in the study. There was a significant difference in the rates of VZV reactivation between the neutrophil recovery and 12 months prophylaxis cohorts at 14 % (n = 11) and 2 % (n = 1) (P = 0.04), respectively. VZV reactivation rate in the 6-month prophylaxis group was 17 % (n = 2), but did not reach statistical significance due to small numbers. In the subset of auto-HCT patients treated with bortezomib, 13 % (n = 2) developed VZV reactivation in the neutrophil recovery group, while no events occurred in the other two cohorts. Complications of VZV reactivation include post-herpetic neuralgia (n = 5), severe pain (n = 3), scarring (n = 1), and motor weakness (n = 1); two patients required hospitalization and three patients developed disseminated zoster. Our limited retrospective analysis suggests a significant reduction in rates of post-auto-HCT rates of VZV reactivation with extended 12 months antiviral prophylaxis. VZV reactivation is a significant complication post-auto-HCT, and extended prophylaxis appears to be safe and effective in this setting.

Low-dose acyclovir prophylaxis for the prevention of herpes simplex virus and varicella zoster virus diseases after autologous hematopoietic stem cell transplantation

“…On the other hand, VZV disease occurs in approximately 16-28 % without long-term prophylaxis [2][3][4][5] and typically presents as a localized dermatomal rash. In addition, disseminated VZV disease, which can result in a fatal outcome [6], and various complications including postherpetic neuralgia and secondary bacterial infections are sometimes observed and may influence the patient's quality of life [2][3][4][5]7]. Therefore, to reduce HSV and VZV disease and their complications, acyclovir prophylaxis has been assessed in several studies.…”

Herpes Zoster in Autologous Hematopoietic Cell Transplant Recipients in the Era of Acyclovir or Valacyclovir Prophylaxis and Novel Treatment and Maintenance Therapies

“…The increasing use of novel chemotherapeutic regimens, T-cell depleting agents (e.g., CD34 selection, Thymoglobulin) and biologics, and maintenance therapies, along with an aging HCT population, poses a heightened risk for infections in this patient population 1–5 . Studies have reported herpes zoster (HZ) as a common infectious complication after autologous HCT in 16%-30% of patients, with most events occurring in the first year after HCT 6–8 .…”

“…In addition to the typical presentation of HZ with a painful dermatomal rash, HCT recipients often experience complications such as post-herpetic neuralgia, ocular disease, and potentially fatal disseminated disease in one-third or more of affected patients 5,9–14 . Given the significant advances in the treatment and supportive care for autologous HCT recipients over the past decade, including the increased use of novel drugs for maintenance therapy after HCT (e.g., bortezomib, lenalidomide) 1,2 , a contemporary understanding of the long-term risk of HZ in this population is important.…”

Duration of Antiviral Prophylaxis and Risk of Herpes Zoster among Patients Receiving Autologous Hematopoietic Stem Cell Transplants: A Retrospective, Observational Study

“…Truong et al [23] carried out a retrospective chart review study among 129 patients undergoing auto-HSCT between January 1, 2004 and January 31, 2010 to analyze rates of VZV reactivation in three different cohorts according to the length of VZV prophylaxis: (1) prophylaxis until neutrophil recovery to ≥500/μL ( n  = 77), (2) prophylaxis for 6 months ( n  = 12), or (3) 12 months ( n  = 40) after auto-HSCT procedure. They found that a significant reduction in rates of VZV reactivation with extended 12-month antiviral prophylaxis (2%) compared to the neutrophil recovery (14%) ( p  = 0.04).…”