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First-Onset Herpesviral Infection and Lung Injury in Allogeneic Hematopoietic Cell Transplantation.

Authors
  • Zhou, Xiaofeng1
  • O'Dwyer, David N1
  • Xia, Meng2
  • Miller, Holly K3
  • Chan, Paul R1
  • Trulik, Kelsey1
  • Chadwick, Mathew M1
  • Hoffman, Timothy C4
  • Bulte, Camille4
  • Sekerak, Kevin4
  • Wilke, Carol A1
  • Patel, Swapneel J5
  • Yokoyama, Wayne M5
  • Murray, Susan2
  • Yanik, Gregory A4
  • Moore, Bethany B1, 6
  • 1 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and.
  • 2 2 Department of Biostatistics, School of Public Health and.
  • 3 3 Department of Hematology/Oncology, Phoenix Children's Hospital, Phoenix, Arizona; and.
  • 4 4 Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan.
  • 5 5 Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
  • 6 6 Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan.
Type
Published Article
Journal
American Journal of Respiratory and Critical Care Medicine
Publisher
American Thoracic Society
Publication Date
Jul 01, 2019
Volume
200
Issue
1
Pages
63–74
Identifiers
DOI: 10.1164/rccm.201809-1635OC
PMID: 30742492
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Rationale: "Noninfectious" pulmonary complications are significant causes of morbidity and mortality after allogeneic hematopoietic cell transplant. Early-onset viral reactivations or infections are common after transplant. Whether the first-onset viral infection causes noninfectious pulmonary complications is unknown. Objectives: To determine whether the first-onset viral infection within 100 days after transplant predisposes to development of noninfectious pulmonary complications. Methods: We performed a retrospective review of 738 allogeneic hematopoietic cell transplant patients enrolled from 2005 to 2011. We also established a novel bone marrow transplantation mouse model to test whether herpesviral reactivation after transplant causes organ injury. Measurements and Main Results: First-onset viral infections with human herpesvirus 6 or Epstein-Barr virus within 100 days after transplant increase the risk of developing idiopathic pneumonia syndrome (adjusted hazard ratio [aHR], 5.52; 95% confidence interval [CI], 1.61-18.96; P = 0.007; and aHR, 9.21; 95% CI, 2.63-32.18; P = 0.001, respectively). First infection with human cytomegalovirus increases risk of bronchiolitis obliterans syndrome (aHR, 2.88; 95% CI, 1.50-5.55; P = 0.002) and grade II-IV acute graft-versus-host disease (aHR, 1.59; 95% CI, 1.06-2.39; P = 0.02). Murine roseolovirus, a homolog of human herpesvirus 6, can also be reactivated in the lung and other organs after bone marrow transplantation. Reactivation of murine roseolovirus induced an idiopathic pneumonia syndrome-like phenotype and aggravated acute graft-versus-host disease. Conclusions: First-onset herpesviral infection within 100 days after allogeneic hematopoietic cell transplant increases risk of pulmonary complications. Experimentally reactivating murine roseolovirus causes organ injury similar to phenotypes seen in human transplant recipients.

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