Reactivation of varicella zoster virus (VZV) can occur in 20-53% of patients during the first year after allogeneic HCT, contributing to a high burden of infectious complications after HCT, and increasing utilization of medical resources and healthcare costs [1]. Accordingly, current guidelines recommend antiviral prophylaxis (e.g., acyclovir) for a minimum of 1 year after HCT, or until discontinuation of immunosuppression, whichever occurs later [1]. The recommended dose of acyclovir (800 mg twice daily [BID]) was derived from at least two randomized studies that demonstrated efficacy (≤5% reactivation) in the first year after HCT [1,2]. However, this strategy is limited by a high risk of nephrotoxicity brought on by the concurrent use of antimicrobials or immunosuppressive medications used to treat graft versus host disease (GVHD) [1]. Currently, there is variability in clinical practice across transplant centers, with studies suggesting short-term efficacy of lower dose acyclovir in solid organ transplant and select patients undergoing HCT [3,4]. As such, VZV prophylaxis at our institution has been acyclovir 400 mg BID, with a duration of at least 1 year after HCT or 3 months after discontinuation of immunosuppressive medications, whichever occurs later. The long-term efficacy of this approach has not been well-described.We conducted a retrospective cohort study of patients who underwent allogenic HCT as adults (≥18 years old) at City of Hope (COH) between January 1, 2010 and December 31, 2015. COH and non-COH medical records were the primary source of information. We abstracted demographic data (age at HCT, sex, race/ethnicity), CMV serostatus, diagnosis (acute myeloid leukemia [AML], acute lymphoid leukemia [ALL], myelodysplastic syndrome [MDS], other), HCT comorbidity-age index (HCT-CI), Karnofsky performance score (KPS), HCT details (donor source, conditioning intensity [5]), relapse risk at HCT [6], severity of acute GVHD, and vital status per an established protocol [7,8]. GVHD prophylaxis was tacrolimus/sirolimus-based or tacrolimus with a short course of methotrexate. Grading of acute GVHD was per established criteria [9]. The Institutional Review Board at COH approved the protocol. Informed consent was provided according to the Declaration of Helsinki.The primary endpoint was VZV infection, categorized as dermatomal (involvement of 1-2 dermatomes) or disseminated (involvement of >2 dermatomes or extracutaneous involvement) per established definitions [10]. Patients were followed until the first episode of VZV infection or a competing risk event, whichever occurred first.Univariate analyses were performed to compare between patients who developed VZV and those who did not. Relapse/ progression or death was considered as a competing event. Time was calculated from the date of HCT to date of death, relapse/progression, or last contact (censored: December 31, 2018). Cumulative incidence of VZV infection was calculated taking into consideration competing risk for right-censored data [11]. Multivariable log...