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Background. Allo-LS is an important complication of HCT. Early RV infection is assumed to be a predictor for allo-LS. We routinely screen patients pre-HCT for RV, both in Nasopharyngeal Aspirate (NPA) and BAL. This study evaluates the impact of RV RNA-DNA-positivity pre-HCT from NPA or BAL respectively on the occurrence of allo-LS.
Methods. We prospectively included all consecutive pediatric HCT recipients from January 2007– October 2013. A PCR on a panel of RV (Adenovirus, Coronavirus, Rhinovirus, RSV, Bocavirus, Influenzavirus A and B, Parainfluenza 1-3 and 2-4, human-Metapneumovirus) was performed on BAL and NPA samples a week prior to HCT. Primary endpoint was allo-LS, defined according to international criteria as Idiopathic Pneumonia Syndrome (acute respiratory symptoms, pulmonary infiltrates, absence of infection) or Bronchiolitis Obliterans (HRCT changes such as air trapping and ground glass, abnormal obstructive pulmonary function test, absence of infection). Cox proportional hazard models were used for analyses.
Results. 178 patients were included, median age 6.8 yr (0.6-22.7), transplanted for leukemia/lymphoma (51%), bone marrow failure syndromes (9%), primary immune deficiency (PID) (18%) and non-PID benign disorders (22%). Myeloablative conditioning regimen was used; chemotherapy based in 85%, containing Total Body Irradiation in 15%. Donors used: Matched family (26%), unrelated cord blood (54%) and unrelated bone marrow (20%). In 57% of patients pre-HCT NPA was positive for RV. RV was detected in 40% of BAL samples. In 37% of NPA-RV positive patients BAL was negative, whereas only 7% of BAL positives were NPA negative. Rhinovirus was the most frequently detected virus (43%). There was a similar distribution of the various viruses in BAL and NPA. Most patients had no or very mild signs of upper respiratory tract infection at time of sampling. In multivariate analyses BAL RV positivity was the only predictor associated with allo-LS: HR 3.89, 95% CI 1.41 – 10.40; p=0.009). NPA-only positivity was not associated with allo-LS (Fig.1) No significant difference was found between Rhino- and nonRhino virus in the risk for allo-LS (Fig.2)
Conclusion. RV positivity is frequently seen in pediatric patients pre-HCT. Rhinovirus was the most commonly found RV. RV positivity in BAL pre-HCT is a strong predictor for allo-LS in children post-HCT. This association was similar for Rhino- and nonRhinovirus positive patients. These data support the importance of identifying patients at risk for allo-LS by pre-HCT BAL. Early recognition may guide preventive strategies: e.g. postponement of elective HCTs and delayed tapering of immune-suppression.
Figure 1. Cumulative incidence of allo-LS for BAL-RV positive, NPA-RV positive and RV negative patients
Figure 2. Cumulative incidence of allo-LS for Rhinovirus positive, non-Rhinovirus positive and RV negative patients.
