Assessment of the Immunodeficiency Scoring Index for Predicting Outcomes After Respiratory Syncytial Virus Infection in Allogeneic Stem Cell Transplant Recipients

Abstract

Respiratory syncytial virus (RSV) is a common cause of respiratory infections in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. The immunodeficiency scoring index (ISI) has shown predictive value in assessing the risk of progression to lower respiratory tract disease (LRTD) and mortality in allo-HCT recipients developing RSV infection but requires further validation in external cohorts. This retrospective study examined RSV episodes in adult allo-HCT recipients from December 2013 to June 2023 at 2 Spanish hospitals. The aim was to validate the predictive value of ISI for LRTD progression and infectious mortality at day +100 after RSV detection and to identify other conditions associated with disease severity. A total of 207 allo-HCT recipients developed 262 episodes of RSV infection, of which 102 (39%) progressed to LRTD. Independent variables significantly associated with LRTD risk were umbilical cord blood transplant [odds ratio (OR) 2.72, P = .016], high-risk ISI (OR 4.4, P = .008), the transplant periods between 2014 and 2016 (OR 0.31, P = .007) and after 2020 (OR 0.13, P = .026), and ribavirin use (OR 0.49, P = .047). The 100-day infectious mortality rate after RSV detection was 8.7%, increasing to 18% in those with LRTD. Variables significantly associated with the risk of mortality were donor/recipient HLA mismatch [hazard ratio (HR) 5.09, P = .011] and absolute lymphocyte count (ALC) [<0.2 × 10^9/L (HR 11.27, P = .003) and 0.2 to 1 × 10^9/L (HR 8.21, P = .008)]. ISI was associated with mortality (HR 6.8, P = .006) only when ALC categories were excluded from the multivariable model. In transplant recipients with RSV infection, a high-risk ISI category is associated with an increased risk of progression to LRTD, whereas ribavirin appears to have a protective role. Mortality in LRTD cases was influenced by HLA mismatch and different levels of lymphopenia, factors which if incorporated may enhance the ISI's ability to predict mortality.