Infection with a respiratory virus before hematopoietic cell transplantation is associated with alloimmune-mediated lung syndromes

Abstract

Background: Alloimmune-mediated lung syndromes (allo-LSs) are life-threatening complications after hematopoietic cell transplantation (HCT). Respiratory virus (RV) has been suggested to play a role in the pathogenesis.

Objective: We studied the relation between RV DNA/RNA detection in the upper/lower airways before HCT and the occurrence of allo-LSs.

Methods: We retrospectively analyzed all HCT recipients between 2004 and 2014, in whom real-time PCR for RV was performed in nasopharyngeal aspirates (NPAs) and bronchoalveolar lavage (BAL) fluid before HCT. The main outcome of interest was the presence of an allo-LS, which was defined as idiopathic pneumonia syndrome or bronchiolitis obliterans syndrome. Other outcomes were overall survival and treatment-related mortality. We used Cox proportional hazard models, logistic regression models, and Fine-Gray competing risk regression for analyses.

Results: One hundred seventy-nine children (median age, 6.8 years) were included. RVs were found in 61% (41% in BAL fluid/NPAs and 20% in NPAs only). Rhinovirus was the most frequently detected RV (42%). Allo-LSs occurred in 13%. RV positivity in BAL fluid was a predictor for allo-LSs (hazard ratio, 3.8; 95% CI, 1.4-10.7; P = .01), whereas RV positivity in NPAs only was not. No other predictors were found. Grade II to IV acute graft-versus-host disease related to steroid treatment shows a trend toward a protective effect (odds ratio, 0.16; 95% CI, 0.0-1.3; P = .08). Allo-LSs significantly increased treatment-related mortality (52% ± 10% in allo-LSs and 20% ± 4% in non-allo-LSs, P = .007).

Conclusions: These results show that pre-HCT BAL fluid RV positivity was a predictor for allo-LSs. Screening for RVs before HCT might identify patients at risk for allo-LSs. This could have implications for prevention and treatment and might subsequently influence the outcomes of HCT.

Keywords: Hematopoietic cell transplantation; alloimmune lung syndromes; bronchiolitis obliterans syndrome; bronchoalveolar lavage; graft-versus-host disease; idiopathic pneumonia syndrome; respiratory virus.