Vaccination as a Key Determinant of Influenza Disease Severity in Allogeneic Hematopoietic Stem Cell Transplant Recipients: An Observational Retrospective Study.

Background: Influenza virus infection remains a major cause of morbidity in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Vaccination is a key preventive strategy; yet, clinical evidence of its benefit in this population is limited. Methods: We conducted a retrospective, multicenter observational study including adult allo-HCT recipients (≥16 years) who developed laboratory-confirmed influenza infection between 2013 and 2023, with the aim of assessing the impact of vaccination on influenza disease severity. Vaccinated status was defined as having received the seasonal influenza vaccine during the same season and before the onset of influenza infection. Results: A total of 143 recipients with 214 influenza episodes were analyzed. The median age was 45 years (range 18-70), and 58% had acute leukemia or myeloid malignancies. Most (64.3%) received transplants from unrelated or haploidentical family donors. Overall, 48 episodes (22%) occurred after influenza vaccination. At infection onset, 52% of vaccinated recipients were profoundly immunosuppressed (within <6 months post-transplant, experiencing active graft-versus-host disease, or receiving immunosuppressors or corticosteroids). Progression to lower respiratory tract disease (LRTD) occurred in 29% of episodes. Multivariable analysis showed influenza vaccination was significantly associated with reduced LRTD risk (HR 0.18; 95% CI: 0.06-0.50; Conclusions: This study provides real-world evidence that seasonal influenza vaccination may reduce disease severity in allo-HCT recipients and confirms the prognostic value of the ISI for disease risk assessment.