Respiratory syncytial virus in hematopoietic cell transplant recipients: factors determining progression to lower respiratory tract disease

J Infect Dis. 2014 Apr 15;209(8):1195-204. doi: 10.1093/infdis/jit832. Epub 2013 Dec 23.

Abstract

Background: Respiratory syncytial virus (RSV) lower respiratory tract disease (LRD) is a life-threatening complication in hematopoietic cell transplant (HCT) recipients. Lymphopenia has been associated with an increased risk of progression from upper respiratory tract infection (URI) to LRD.

Methods: This study retrospectively analyzed the significance of lymphocyte engraftment dynamics, lung function, smoking history, corticosteroids, antiviral treatment, viral subtypes, and RSV-specific neutralizing antibodies for the progression to LRD in 181 HCT recipients with RSV URI.

Results: In multivariable models, smoking history, conditioning with high-dose total body irradiation, and an absolute lymphocyte count (ALC) ≤100/mm(3) at the time of URI onset were significantly associated with disease progression. No progression occurred in patients with ALCs of >1000/mm(3) at URI onset. Lymphocyte engraftment dynamics were similar in progressors and nonprogressors. Pre- and posttransplant donor and posttransplant recipient RSV subtype-specific neutralizing antibody levels, RSV viral subtypes, and corticosteroids also were not significantly associated with LRD progression.

Conclusions: Host and transplant related factors appear to determine the risk of progression to LRD more than viral factors. Dysfunctional cell-mediated immunity appears to be important in the pathogenesis of progressive RSV disease after HCT. A characterization of RSV-specific T-cell immunity is warranted.

Keywords: Hematopoietic cell transplantation; Respiratory syncytial virus; Respiratory tract disease; Respiratory virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Glucocorticoids / therapeutic use
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunity, Cellular / immunology
  • Infant
  • Male
  • Middle Aged
  • Neutralization Tests
  • Respiratory Syncytial Virus Infections / diagnosis*
  • Respiratory Syncytial Virus Infections / drug therapy
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Viruses / pathogenicity*
  • Respiratory Tract Diseases / diagnosis*
  • Respiratory Tract Diseases / drug therapy
  • Respiratory Tract Diseases / virology
  • Retrospective Studies
  • Risk Factors
  • Young Adult

Substances

  • Antiviral Agents
  • Glucocorticoids