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

## TL;DR

This study shows that seasonal influenza vaccination reduces disease severity in patients who received stem cell transplants.

## Contribution

The study provides real-world evidence that influenza vaccination lowers disease severity in allogeneic stem cell transplant recipients.

## Key findings

- Vaccination reduced progression to lower respiratory tract disease and hospitalization risk.
- The immunodeficiency scoring index predicted higher disease severity and admission risk.

## Abstract

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.

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.

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; P = .001), while a high-risk immunodeficiency scoring index (ISI) (HR 4.71; 95% CI: 1.99–11.17; P = .0004) and fever at screening (HR 2.16; 95% CI: 1.51–3.08; P < .001) independently predicted higher LRTD risk. Vaccination was also associated with decreased hospitalization risk (OR 0.20; 95% CI: 0.05–0.57; P = .005); whereas, high-risk ISI was linked to higher admission risk (OR 22.86; 95% CI: 4.82–170, P = .0003).

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.

Among 143 allogeneic hematopoietic stem cell transplantation recipients with influenza, vaccination independently reduced progression to lower respiratory tract disease and hospitalization. The immunodeficiency scoring index stratified risk, reinforcing vaccination and early risk assessment as central components of clinical management.