S1639 safety and efficacy of live attenuated varicella vaccine for preventing varicella zoster virus disease after allogeneic hematopoietic stem cell transplantation: a prospective single-center study

Background: Varicella‐zoster virus (VZV) disease commonly occurs after allogeneic hematopoietic stem cell transplantation (allo‐HCT). Although long‐term acyclovir prophylaxis can prevent reactivation of VZV during acyclovir administration, VZV disease still remains a major problem after discontinuation of acyclovir. Thus, reconstitution of VZV‐specific T‐cell immunity may be necessary for allo‐HCT patients to prevent VZV disease completely. Vaccination against VZV has been considered as the method for accelerating VZV‐specific immune recovery. However, limited data is available on VZV vaccination after allo‐HCT. Aims: We conducted a single‐center, single‐arm, prospective study to evaluate safety and efficacy of live attenuated varicella vaccine for preventing VZV disease in adult patients who underwent allo‐HCT. Methods: Patients without active chronic GVHD, relapse and ongoing immunosuppressive therapy at 2 years after allo‐HCT were eligible for this study. We administered a single dose of live attenuated varicella vaccine (Biken, Osaka, Japan) to the enrolled patients. The primary endpoint was cumulative incidence of VZV disease after vaccination. Secondary endpoints were adverse effect of vaccine, and evaluation of VZV antibody titer and VZV specific T‐cells before and after vaccination. Immunoglobulin G (IgG) antibody titers against VZV were measured by enzyme immunoassay (EIA) using patient plasma. IgG index value of equal to or greater than 4 was considered positive. This study was approved by the institutional review boards of Jichi Medical University. Written informed consent was obtained from all patients in accordance with the Declaration of Helsinki. The study was registered at UMIN Clinical Trials Registry (UMIN000013799). Results: A total of 25 adult patients were enrolled in this study. The cumulative incidences of VZV disease at 1 and 2 years after vaccination were both 20.0% (95% confidence interval (CI), 2.7–34.2%). Six patients developed VZV disease (zoster) at a median of 224 days (range 89–874) after vaccination. No adverse events associated with varicella vaccine were observed. The median VZV IgG titers were 3.8 (range <2 ‐ 82.2) before vaccination and 5.2 (range <2 ‐ 56.9) at 1 month after vaccination. To predict the development of VZV disease after vaccination, we defined some cut off values of lymphocyte and IgG using the receiver‐operating characteristics curve. The lower CD4 + T‐cell count (≤468/μL) and CD4/CD8 T‐cell ratio (≤0.53) at the time of vaccination groups significantly experienced VZV disease at 2 years after vaccination (28.6% vs 0%, p = 0.036, and 44.4% vs 0%, p = 0.0020, respectively). In addition, the lower VZV IgG (≤8.1) at 1month after vaccination was also associated with higher incidence of VZV disease (29.4% vs 0% at 2 years, p = 0.062). Summary/Conclusion: The current study indicated that a single dose of live attenuated varicella vaccine was safe and effective for preventing VZV disease in adult allo‐HCT patients. However, the effect was insufficient for some patients. Therefore, additional strategies, such as the administration of at least 2 dose of varicella vaccine, may be necessary to eradicate VZV disease.