Immunogenicity of early revaccination after allogeneic stem cell transplantation using post-Transplantation Cyclophosphamide as GVHD prophylaxis.
Revaccination is indicated for all recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in order to restore immunological memory and to prevent infectious complications post-HSCT. Current guidelines recommend to start revaccination 3-4 months post-HSCT, provided the absence of contraindications. However, the optimal starting point, predictors for response, and immunogenicity of this early starting schedule have not been determined as existing data show mixed results. Additionally, the post-HSCT population is extensively heterogeneous. Subsequently, post allo-HSCT patients likely benefit from a personalized approach using predictive biomarkers to determine the optimal starting point. Therefore, we performed a retrospective analysis of the response to revaccination and of immunological and clinical factors that potentially influence this response in a large cohort of allo-HSCT patients all receiving post-Transplantation Cyclophosphamide as GVHD prophylaxis.
This retrospective single center cohort study assesses the immunogenicity (IgG) of pneumococcal, meningococcal type C (Men-C), and Haemophilus influenzae type b (Hib) revaccination starting 3-4 months post allo-HSCT. In addition, presence of clinical variables and levels of immunological reconstitution parameters (prior to (T0) and 5-6 months after start vaccination(T1)) were compared between vaccine-responders versus non-responders. Patients with allo-HSCT (between 01-2020 and 12-2024) were included if they had received the revaccination schedule plus serological evaluation (12 months post-vaccination) and if they participated in the LUMC Hematological Diseases Biobank.
Between 01-2020 and 12-2024, 344 patients received allo-HSCT using pTCy in the LUMC, of these 233 had available serological evaluation after revaccination, 160 of these were included in the biobank, and 116 received vaccinations from 3-4 months post-HSCT. Patients for whom revaccination was started 3-4 months post allo-HSCT (n=116) had an overall pneumococcal response of 31.9% (primary outcome). Of these patients, 11.2% and 42.2% responded to serotypes present only in PPV23 and in both pneumococcal vaccines, respectively. Patients with a response to pneumococcal vaccination (overall and serotypes only present in PPV23) had significantly higher IgG prior to (T0) and B cell count during the vaccination period (T1). Responses to men-C and Hib vaccination were 87.3% and 83.3%, respectively (measured in 55 and 72 patients).
When revaccination is started at 3-4 months post allo-HSCT 31.9% of patients respond adequately to the current pneumococcal vaccination schedule. Immunogenicity of PPV23 is particularly poor with only 11.2% responding to all PPV23-serotypes. Our results suggest that B cell functionality, measured as a proxy in total B cell count and IgG production, could be an important determinant for adequate vaccine response.