An Immune Recovery-Based Revaccination Protocol for Pediatric Hematopoietic Stem Cell Transplant Recipients: Revaccination Outcomes Following Pediatric HSCT

Following hematopoietic stem cell transplant (HSCT), patients are at increased risk of vaccine-preventable diseases (VPDs) and experience worse outcomes of VPDs compared to immunocompetent patients. Therefore, patients are routinely vaccinated post-HSCT to restore VPD immunity. Published guidelines recommend revaccination based on time post-HSCT, although optimal revaccination timing and the value of using other clinical and laboratory variables to guide revaccination remain unclear. An institutional immune recovery-based protocol to guide timing of revaccination is used at Children's Hospital Colorado. This protocol incorporates time from transplant, time off immunosuppressive therapy and intravenous immunoglobulin replacement, absence of active graft-versus-host disease (GVHD), and minimum absolute CD4 count, absolute lymphocyte count (ALC), and immunoglobulin G (IgG) levels. The objective of this study is to evaluate the performance of this immune recovery-based revaccination protocol by determining rates of seroprotective vaccine responses achieved and describing demographic, clinical, and laboratory markers associated with protective antibody titers post-revaccination. Rates of seroprotection following revaccination were retrospectively determined for patients who received autologous or allogeneic HSCTs at Children's Hospital Colorado from 2007 to 2017. Percent seropositivity after revaccination was determined for ten VPDs: measles, mumps, rubella, varicella, tetanus, diphtheria, Haemophilus influenzae type B (Hib), poliovirus, hepatitis B virus (HBV), and Streptococcus pneumoniae. The impact of covariates, including post-HSCT vaccine timing, patient demographics, clinical features (diagnosis, donor and conditioning regimen data, GVHD, cytomegalovirus disease), and laboratory parameters (CD4 count, ALC, IgG level), on rates of seroprotection post-revaccination was determined using Wilcoxon rank sum, Fisher's exact, or chi-square tests, as appropriate. One hundred-twelve unique patients among 427 HSCT recipients had available data for both revaccination timing and vaccine titers. Among these, high rates of seroprotection were achieved after revaccination for rubella (100%), diphtheria (100%), tetanus (100%), and Hib (98%). More modest rates of seroprotection were achieved after revaccination with HBV (87%) and pneumococcal conjugate (85%) vaccines. Seroprotection was lower after revaccination with measles (76%), pneumococcal polysaccharide (72%), mumps