Factors Affecting Immune Reconstitution Post‐Allogeneic HSCT in Children: The Case for an Individualized Approach to Vaccination

Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used to treat malignant and non-malignant diseases. Following allogeneic HSCT, patients are particularly vulnerable to vaccine-preventable diseases (VPD) because conditioning depletes immune cells, including memory cells. Revaccination is therefore essential, but multiple factors, such as conditioning regimen, stem cell source, HLA compatibility, graft-versus-host-disease (GVHD), and age, affect immune reconstitution and vaccine response. Current guidelines recommend uniform vaccination schedule for all allogeneic HSCT patients, despite this heterogeneity. In this review, we discuss how these factors influence immune reconstitution and vaccine response, and highlights the need for a more individualized approach. Based on current evidence, we propose that vaccine timing, particularly for inactivated vaccines, could benefit from adjustment according to immune recovery markers, such as lymphocyte counts and presence of GVHD, rather than relying on fixed post-HSCT timepoints. We also discuss emerging immunotherapies, including CAR-T cells and bispecific antibodies, which can induce similarly prolonged immunosuppression and may benefit from personalized vaccination strategies. Further studies in pediatric populations are needed to define immunological threshold that would enable safer and more effective personalized vaccination schedules.