Antibody responses to re-immunization in recipients of allogeneic hematopoietic cell transplantation

Abstract Background Immunologic memory against vaccine-preventable diseases is often lost after an allogeneic hematopoietic cell transplant (allo-HCT), therefore recipients are required to be re-immunized after allo-HCT to regain immunity against these infections. But the response to vaccination after an allo-HCT can be highly variable and is not well understood. We performed a single center retrospective study to examine immunization practices and determine the rate of vaccine protection and seroconversion following vaccination after allo-HCT. Methods Electronic medical records (EMR) from patients ≤18 years of age who underwent allo-HCT at St. Jude Childrens’ Research Hospital between 2005 - 2021 were reviewed. Clinical information and serology results before and after completion of the immunizations series were extracted from the EMR. The vaccines included in this analysis were diphtheria, measles, mumps, rubella (MMR), varicella, and polio. Protection was evaluated only for infections with established immune correlates. Seroconversion was defined as 4-fold increase in titers for vaccines with quantitative antibody assays, or as a change from negative to positive IgG for vaccines with qualitative antibody tests. Results 760 patients were included in this cohort. Demographic and clinical data are summarized in Table 1. The mean age at allo-HCT was 10.4 years, most were male (56.8%) and white (74.6%). Acute leukemia accounted for 66.4% of allo-HCT recipients. Conditioning was myeloablative for 53.45%, and reduced intensity for 37.9%. Most received transplants from mismatched-related donors, (44.9%), followed by matched unrelated donors (35.4%) and matched related donors (19.5%). The number of patients who received the full vaccination series at our institution differed by vaccine and ranged from 41-150, and the respective subsets with available pre-vaccination and post-vaccination titers ranged from 24-93. The median time from transplant to initiation of immunizations was 12 months (range: 6-58) for non-live vaccines, 25 months (range: 23, 63) for MMR vaccine, and 28 months (range: 16, 117)) for varicella vaccine. Protection post immunization varied, with less patients demonstrating protections for mumps (79%) and measles (82%) (Figure 1). Seroconversion also varied among the different vaccine components and types of vaccines. Conclusion Current strategies to re-immunize patients after allo-HCT do not provide protection to all patients. Understanding the factors associated with suboptimal immune responses is critical for advancing our knowledge in this area. Whether time-based approaches combined with immune reconstitution data are required to further optimize protection remains unclear. Additionally, different vaccine schedules (i.e., higher doses) may be required in these patients. Figure 1. Protection and seroconversion rate by vaccine target.