Risk factors for molecular detection of adenovirus in pediatric hematopoietic stem cell transplantation recipients

Biol Blood Marrow Transplant. 2012 Aug;18(8):1227-34. doi: 10.1016/j.bbmt.2012.01.013. Epub 2012 Jan 25.

Abstract

Adenovirus (AdV) infections are a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). To evaluate the use of molecular AdV testing in HSCT at our institution and identify risk factors for AdV viremia and disease, we performed a retrospective cohort study of all HSCT recipients who had undergone AdV polymerase chain reaction testing over a 2-year period. Two cohorts were identified: cohort 1, comprising patients testing positive for AdV (n = 7) and cohort 2, comprising patients testing negative (n = 36). Overall patient characteristics were not statistically significantly different between the 2 cohorts. A comparison of cohort 1 and cohort 2 identified the following medication exposures as risk factors influencing AdV status: preparatory regimens using fludarabine (relative risk [RR], 8.73; 95% confidence interval [CI], 1.18-64.27; P = .006), melphalan (RR, 3.47; 95% CI, 0.76-15.94: P = .08), and/or cyclophosphamide (RR, 0.18; 95% CI, 0.02-1.4; P = .05), and GVHD prophylaxis with methylprednisone (RR, 3.73; 95% CI, 1.01-13.9; P = .04). AdV-positive patients had higher grades of GVHD and higher rates of GVHD of the gastrointestinal tract (RR, 4; 95% CI, 1.18-13.5; P = .03) compared with AdV-negative patients. Four of the 7 AdV-positive patients had concomitant clinical manifestations of disease, including pneumonia, diarrhea, and/or disseminated disease. Clinical outcomes in symptomatic patients included resolution of disease in 2 patients and death in 2 patients. All 7 AdV-positive patients received antiviral therapy, including 1 patient with severe disseminated disease that resolved after administration of liposomal cidofovir. Our study at a large pediatric HSCT center provides important preliminary data for the development of a prospective trial destined to identify specific HCST patient subpopulations that might benefit most from molecular screening and early preemptive therapy.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / isolation & purification*
  • Adenoviridae Infections / etiology*
  • Adenoviridae Infections / virology
  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Infant
  • Male
  • Retrospective Studies
  • Risk
  • Risk Factors