Single-Center Study of Human Herpesvirus 6B Detection in Bronchoalveolar Lavage Fluid After Hematopoietic Cell Transplantation

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In a single-institution study reported in the Journal of Clinical Oncology, Hill et al found that detection of human herpesvirus 6B (HHV-6B) in bronchoalveolar lavage fluid was associated with increased mortality in recipients of allogeneic hematopoietic cell transplantation (HCT) with lower respiratory tract disease.

Study Details

The study involved assessment of bronchoalveolar lavage fluid for HHV-6B DNA using polymerase chain reaction in 553 patients at Fred Hutchinson Cancer Research Center receiving allogeneic HCT who underwent bronchoalveolar lavage for evaluation of lower respiratory tract disease between 1992 and 2015. Eligible patients had to have stored bronchoalveolar lavage fluid samples within 100 days after HCT.

Outcomes by HHV-6B Status

Bronchoalveolar lavage fluid was HHV-6B–positive in 147 of the 553 patients (27%). In multivariate analysis, risk of overall mortality (adjusted hazard ratio [aHR] = 2.18, 95% confidence interval [CI] = 1.41–3.39) and risk of death from respiratory failure (aHR = 2.50, 95% CI = 1.56–4.01) were significantly increased in patients with HHV-6B–positive bronchoalveolar lavage fluid (with or without co-pathogens) vs those with HHV-6B–negative bronchoalveolar lavage fluid.


  • Bronchoalveolar lavage fluid was HHV-6B–positive in 27% of tested patients.
  • Patients with HHV-6B–positive BALF had increased risk of overall mortality and death from respiratory failure.

Patients with HHV-6B–positive bronchoalveolar lavage fluid who received antivirals within 3 days prior to bronchoalveolar lavage had lower median HHV-6B bronchoalveolar lavage fluid viral load (approximately one log10 reduction) vs those who did not receive antivirals; those who received antivirals had a numerically lower risk of overall mortality (aHR = 0.42, 95% CI = 0.16–1.10). 

Among three patients with HHV-6B–positive bronchoalveolar lavage fluid and sufficient tissue RNA preservation, all had intraparenchymal HHV-6 gene expression detected by RNA in situ hybridization in lung tissue.

The investigators concluded, “These data provide evidence that HHV-6B detection in [bronchoalveolar lavage fluid] is associated with higher mortality in allogeneic hematopoietic cell transplantation recipients with [lower respiratory tract disease]. Definitive evidence of causation will require a randomized prevention or treatment trial.”

Joshua A. Hill, MD, of Fred Hutchinson Cancer Research Center, is the corresponding author of the Journal of Clinical Oncology article.

Disclosure: The study was supported by National Institutes of Health grants, American Society for Blood and Marrow Transplantation, and a Dharam Ablashi Research Fund Grant from the HHV-6 Foundation. For full disclosures of the study authors, visit

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