Respiratory Virus prior to Hematopoietic Cell Transplantation is associated with allo-immune mediated lung syndromes

Publication date: Available online 15 July 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Birgitta Versluys, Marc Bierings, Jean Luc Murk, Tom Wolfs, Caroline Lindemans, Kors vd Ent, Jaap Jan Boelens
BackgroundAllo-immune mediated lung syndromes (allo-LS) are life-threatening complications after hematopoietic cell transplantation (HCT). Respiratory virus (RV) has been suggested to play a role in the pathogenesis.ObjectiveWe studied the relation between RV-DNA/RNA detection in upper/lower airway before HCT and the occurrence of allo-LS.MethodsWe retrospectively analyzed all HCT recipients between 2004 and 2014, in whom Real-Time PCR for RV was done from Nasal-Pharyngeal-Aspirates (NPA) and Broncho-Alveolar- Lavage (BAL) before HCT. Main outcome of interest was allo-LS, defined as Idiopathic Pneumonia Syndrome or Bronchiolitis Obliterans Syndrome. Other outcomes were overall survival and treatment related mortality (TRM). We used Cox proportional hazard models, logistic regression models and Fine-Gray competing risk regression for analyses.Results179 children (median age 6.8 years) were included. RV was found in 61% (41% in BAL/NPA, 20% in NPA-only). Rhinovirus was the most frequently detected RV (42%). Allo-LS occurred in 13 %. RV-positivity in BAL was a predictor for allo-LS (HR 3·8, 95% CI 1·4 – 10·7; p=0·01), while RV-positivity in NPA-only was not. No other predictors were found. Acute Graft-Versus-Host-Disease grade 2-4, related with steroid treatment, shows a trend towards a protective effect (OR 0·16, 95%CI 0·0–1·3; p=0·08). Allo-LS significantly increased TRM (52 ± 10% in allo-LS, 20 ± 4% in non-allo-LS, p= 0·007).ConclusionsThese results show that pre-HCT BAL RV-positivity was a predictor for allo-LS. Screening for RV before HCT may identify patients at risk for allo-LS. This may have implications for prevention and treatment and may subsequently influence the outcomes of HCT.

Graphical abstract



This study shows a strong relation between Respiratory Virus prior to transplant, and alloimmune lungsyndromes, which may have therapeutic implications. Our hypothesis, based on biological and pathophysiological factors, can guide reflections on immunemediated disease in general.


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