Adenovirus infection in hematopoietic stem cell transplantation: effect of ganciclovir and impact on survival

Abstract

Adenoviruses (ADV) are emerging as important causes of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). In mainly non-T-cell depleted HSCT recipients, we analyzed the incidence of ADV infection, risk factors for infection, the effect of ganciclovir administered for prevention of cytomegalovirus (CMV), and the impact of ADV infection on survival. The overall incidence of ADV, irrespective of the method of detection, was 8.5% (450/5233) and 12.3% (43/348) after the first or second allogeneic HSCT, and 6.3% (78/1219) and 6.5% (5/77) after the first or second autologous HSCT, respectively. The most frequent sites of infection and disease were stool and gastrointestinal tract, respectively. Statistically significant risk factors associated with ADV infections among allogeneic recipients included younger age, grade II to IV graft-versus-host disease, year of transplantation, and a second allogeneic HSCT. Furthermore, allogeneic patients seronegative for CMV at transplantation and seropositive allogeneic patients who did not receive ganciclovir, either at engraftment or as pre-emptive therapy on CMV reactivation, were at higher risk of developing ADV infections compared with seropositive patients who received ganciclovir (odds ratio=1.8, 95% confidence interval (CI) 1.2 to 2.8, P=.005 and odds ratio=3.4, 95% CI 2.1 to 5.55, P<.0001, respectively). The hazard of overall mortality was higher in patients who contracted ADV compared with those who did not (hazard ratio 1.5, 95% CI 1.3 to 1.7, P<.0001). This study shows that ADV infections are associated with poor transplantation outcome in T-cell repleted HSCT recipients. Ganciclovir, given for CMV prevention, may have a protective effect. Controlled treatment and prevention studies are warranted.