Outcome of Repeated Vaccination to Hepatitis B Virus in Patients Failing to Respond to Vaccination Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): If at First You Don't Succeed, Try Try Again

Background: Recipient immunity is compromised after HSCT, obligating patients (pts) to take prophylactic antimicrobial and antiviral agents and to be reimmunized to viral and bacterial pathogens. Hepatitis B virus (HBV) infection is a major public health problem, with about 30% of the world population having serological evidence of current or past HBV infection. HBV vaccination post-HSCT is imperative in these pts, as most lose protective HBV surface antibodies (anti-HBs) following conditioning, placing them at high risk for HBV reactivation. Guidelines recommend delaying vaccination (including HBV) for 6-12 months following transplantation to allow for cellular and humoral immune recovery. Even with delaying vaccination, immunosuppression, graft-versus-host disease (GVHD), and delayed immune reconstitution hinder the effectiveness of vaccines. The efficacy of HBV vaccination is not well defined in pts on immunosuppressive therapy (IST) and/or in those with GVHD. Further, little data exists on the efficacy of HBV revaccination in pts failing to respond to the 1st vaccination series. We studied factors impacting the success of vaccination in pts undergoing one to four HBV vaccination series after HSCT. Methods: This single-center, retrospective study evaluated the effectiveness of HBV vaccine in HSCT pts by assessing protective antibody generation after vaccination. Fifty-two pts (25 female, 27 male) who received at least one 3-dose HBV vaccination series post-HSCT and who had evaluable post-vaccine anti-HBs titers were included in the analysis. Pts with negative or indeterminate anti-HBs titers following the first vaccine series were eligible to receive one or more additional series of HBV vaccinations. All pts were treated with cyclophosphamide and fludarabine based conditioning (± anti-thymocyte globulin) and received GVHD prophylaxis with either cyclosporine/tacrolimus with or without mycophenolate mofetil. The vaccine response rate over a series of vaccinations was estimated by Kaplan-Meier methods. The development of response after the first vaccination was correlated with patient baseline and post-HSCT factors including pretransplant HBV titers, vaccination time post-transplant, use of rituximab and IST and absolute lymphocyte count (ALC), CD4, and CD8 cell counts and history of acute or chronic GVHD. Results: The studied cohort included 52 HSCT pts with a median age of 22 years (range 7-62) and a variety of diagnoses (38 aplastic anemia, 6 myelodysp