Herpes zoster frequency and adjuvanted recombinant zoster vaccination after allogeneic hematopoietic cell transplantation

Abstract

Background: The prevention of Herpes Zoster (HZ) is of prime importance in patients post allogeneic hematopoietic cell transplantation (alloHCT). Shingrix, an inactivated, adjuvanted recombinant zoster vaccine (aRZV) is now available and recommended to prevent HZ in seropositive immunocompromised patients. Safety and efficacy for this vaccine has been established in autologous HCT and other immunocompromised patients, however, for alloHCT recipients, limited data exists.

Objectives: The primary outcome was the frequency of HZ occurring in patients post alloHCT in those who received aRZV vaccination compared with those who did not receive aRZV. Other characteristics of interest included the clinical presentation of HZ, treatment, and outcomes related to the HZ episode.

Study design: A single-center retrospective observational cohort study was conducted at Princess Margaret Hospital, Toronto, Canada between April 1 2018 - May 1 2024. Adult patients were included from a prospective registry if they underwent alloHCT from April 1 2018 - Dec 31 2022. Follow up was censored at time of death, 90 days post first episode of HZ, loss to follow-up, end of study period or 36 months post alloHCT. Data was systematically collected from the electronic medical record or registry. A confirmed HZ episode was defined by clinical and/or molecular criteria. Statistical analysis was performed to determine risk factors associated with HZ and the relative risk (RR) of HZ episode occurring in those ≥ 12 months post HCT considering aRZV status and cumulative follow-up period.

Results: In total 445 patients were included. Median age was 56-years-old (interquartile range, IQR, 38 - 64), with slight male predominance (241/445, 54.2%). From ≥ 12 months post alloHCT, there were 43 HZ episodes, with 26/263 (9.9%) in patients who had received at least one dose of aRZV, 19/263 (7.2%) after two doses, 7/70 (10.0%) in those who had not received aRZV and 10/112 (8.9%) with unknown vaccination status. Median time to HZ post any dose of aRZV was 8.1 months (IQR 3.9 - 12.3). Overall, median time to HZ episode post alloHCT was 20.7 months (IQR 16.9 - 27.9), the majority occurring after antiviral prophylaxis cessation (38/43, 88.4%). Most HZ episodes were localized (38/43, 88.4%), treated in the outpatient setting with oral antiviral therapy (39/43, 90.7%) for a median of 10 days (IQR 7 -14). There was no disseminated HZ in those who had received aRZV. Considering aRZV status and follow-up period, the RR of HZ in those who had received two doses of aRZV compared to those who had not received any doses of aRZV was 0.90 (95% Confidence Interval 0.75-1.07, p = 0.22). In a sensitivity analysis, the risk of HZ was reduced (lower RR) in those receiving aRZV ≥ 12 months post-HCT compared with those who did not receive aRZV.

Conclusions: Overall, the receipt of aRZV did not seem to influence the frequency of HZ in patients post alloHCT, however, there may be disease severity modification and benefit if receiving beyond 12 months post HCT. We provide preliminary findings that would benefit from further evaluation in a prospective, randomized trial.

Keywords: hematopoietic cell transplantation; herpes zoster virus; immunocompromise; vaccination.