Molecular monitoring of adenovirus in peripheral blood after allogeneic bone marrow transplantation permits early diagnosis of disseminated disease

Abstract

Adenovirus (AdV) infection in the course of allogeneic stem cell transplantation (SCT) is associated with high transplant-related morbidity and mortality. Disseminated AdV disease is lethal in most instances. Early detection of AdV infection and identification of patients carrying a high risk of disseminated disease therefore remain a major challenge. In view of the large number of existing AdV types, we have established real-time polymerase chain reaction (PCR) assays permitting sensitive detection and quantification of all 51 currently known human AdV serotypes. In a series of 132 consecutive pediatric patients undergoing SCT, more than 5000 samples derived from peripheral blood (PB), stool, urine, and throat were screened for adenovirus infection by PCR during the posttransplantation period. Thirty-six patients (27%) tested positive by PCR, revealing AdV types of the subgenera A, B, C, D, and F. Except for enteritis in some patients with AdV positivity in stool, detection of the virus at sites other than PB was not associated with clinical signs of virus disease, and transplant-related mortality was not significantly different from AdV-negative patients. By contrast, 82% of patients who had detectable AdV in PB died from infectious complications (P <.001). Monitoring of PB specimens by real-time PCR permitted early diagnosis of invasive AdV infection in all instances. In patients who developed disseminated AdV disease, detection of the virus in PB preceded onset of clinical symptoms by a median of more than 3 weeks. The observation of AdV in peripheral blood may therefore serve as a basis for early initiation of preemptive antiviral treatment.