Evaluation of Varicella Zoster Prophylaxis after Allogeneic Hematopoietic Cell Transplantation Using Valacyclovir Followed By Vaccination
Authors: Jamani Kareem , Daly Andrew , Storek Jan 
Published: October 2019

Rationale: Varicella zoster virus (VZV) disease occurs frequently post allo-HCT. While cutaneous disease is often complicated by debilitating post-herpetic neuralgia (PHN), visceral or CNS disease can be fatal. Studies have demonstrated that VZV disease is reduced during prophylaxis with acyclovir; however, patients frequently develop VZV disease after discontinuation of acyclovir. Recently, the varicella vaccine has been found to be safe and immunogenic post allo-HCT. The optimal prophylactic strategy for VZV disease post allo-HCT has not been established. Here we present a retrospective single-center study, comparing pre-2007 prophylaxis, which consisted of less than 2 years of post allo-HCT acyclovir, with post-2007 prophylaxis, which consisted of 2 years of valacyclovir prophylaxis followed by live attenuated varicella vaccination.
Objective: To evaluate the hypothesis that the cohort treated with the pre-2007 strategy ("old strategy") had a higher cumulative incidence of VZV disease and PHN compared to the cohort treated with the post-2007 strategy ("new strategy").
Methodology: Charts of patients undergoing allo-HCT in Calgary between January 2004 and June 2011 were reviewed. VZV disease was defined as clinical zoster or visceral/CNS disease confirmed by immunostain or PCR. PHN was defined as pain in the affected dermatome persisting more than 3 months after the onset of the rash. Cumulative incidence of VZV disease and PHN were compared using competing risks regression (Fine-Gray), treating relapse, graft failure, second malignancy and death as competing risks.
Results: 482 patients underwent first allo-HCT in Calgary during the review period. 21 were excluded due to inadequate data. 119 were treated with the new strategy, 116 with the old strategy and 226 experienced a competing event while on prophylaxis. Some patients in the old strategy group received late VZV vaccination (at >2 years). The old strategy was associated with a trend towards higher cumulative incidence of VZV disease (sHR 1.57, 95% CI 0.95-2.62, p=0.08) and with significantly higher cumulative incidence of PHN (sHR 9.94, 95% CI 1.24-80.05, p=0.03). 3 episodes of VZV disease in the old strategy group and 7 episodes in the new strategy group were associated with deviation from protocol (most associated with medication noncompliance). When events associated with protocol deviation were excluded, the old strategy led to a significantly higher cumulative incidence of VZV disease (HR 2.40, 95% CI 1.32-4.38, p=0.004) and PHN was not observed in the new group (p= <0.01). Vaccination was safe; however 10% of patients developed immediate or late cutaneous VZV disease. PHN was not observed in the patients who developed the VZV disease post vaccination.
Conclusions: The new strategy was associated with a trend towards less VZV disease and significantly less PHN. Noncompliance was a significant contributor to VZV disease in the new strategy group. If compliance is ensured, the new strategy significantly reduces VZV disease and eliminates PHN.

Disclosures
No relevant conflicts of interest to declare.