Trend, Risk Factors and Outcome of Respiratory Syncytial Viral Infection in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Multi-Institutional Review

Introduction: Respiratory syncytial virus (RSV) is a common cause of serious respiratory infections in hematopoietic stem-cell transplant (HSCT) recipients. Infection of the upper airways may progress to lower airway leading to mortality especially in young children. In spite of being a common infection, there is paucity of data about its prevalence, efficacy of prevention, risk factors for infection and mortality in pediatric HSCT recipients.

Methods: We used the Pediatric Health Information System (PHIS), an electronic database of children's hospitals in the US. Patients under the age of 21 who underwent HSCT at one of the 42 PHIS hospitals from 2000-2013 were analyzed. We abstracted data on demographics, hospitalizations, medications, RSV and other HSCT related complications. 

Results: From 2000 to 2013, a total of 13795 unique pediatric patients who received HSCT were identified. Among these 1023 (7.4%) children were identified to have the diagnosis of RSV.  Out of 1023 children with RSV, 19% required ICU care and 14% required mechanical ventilation. Overall, the trend of RSV diagnosis was stable in our cohort (Figure 1). The demographic characteristics, risk factors and outcome of these children with and without RSV are shown in Figure 2.  RSV was significantly associated with allogeneic HSCT (p=<0.001), CMV (p= <0.001), fungal infection (p=<0.001) and GVHD (p=<0.001). Prophylactic Pavilizumab was associated with lower risk of RSV only in patients <1 year of age (24% vs. 76%, p=<0.0001). The mortality was significantly higher in patients with RSV compared to those without (18.6% vs. 11.4%, p <0.001). However, there was no difference in median time (days) to mortality following HSCT in patients with or without RSV (1427 [615, 2769] vs. 1554 [613, 3038], p=0.1).  Multivariate logistic regression analysis of age, gender, HSCT type, CMV, GVHD, concurrent viral and bacterial respiratory infections, Pavilizumab, IVIG, Respigam and Ribavirin showed only older age i.e. ≥10 years at the time of HSCT [HR 2.17 (1.35, 3.48), p=<0.001], GVHD [HR 1.36 (1.01, 1.84), p=0.041] were associated with increased mortality whereas the use of IGIV [HR 0.74 (0.54, 0.99), p=0.049] was protective in patients with RSV (Figure 3). 

Conclusions: Ours is the largest cohort of RSV following HSCT in children with the prevalence of 7.4%. The mortality in our pediatric cohort is 18.6% which is similar to previously publishes case series. Older patients, GVHD were associated with increased mortality whereas Pavilizumab not associated with improved survival in our study. Further studies are needed to explore effective RSV prophylactic strategies and the use of novel therapies to optimize the outcome.

Figure 1: RSV trend in pediatric HSCT recipients

p = 0.8

Figure 3A: Overall mortality in HSCT recipients

Figure 3B: Mortality among RSV patients (Age)