Cidofovir Is Safe and Effective in the Treatment of Adenoviral Infection in Pediatric Hematopoietic Stem Cell Transplantation.

Adenovirus (ADV) infections are increasingly recognized as significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Early diagnosis and prompt initiation of effective treatment are important in preventing often fatal disseminated ADV disease. We report our experience with using cidofovir (CDV) for the treatment of adenovirus infection in 57 HSCT patients, median age 8 years (range 0.5–26). Fifty-four patients received allogeneic HSCT, 35 of whom were T-cell depleted with 3 patients receiving autologous marrow. Blood was tested weekly for ADV by quantitative real-time PCR, with viral culture performed on urine, stool and throat swabs. Antiviral therapy was initiated immediately upon detection of ADV by PCR, culture or tissue histopathology. Cidofovir was given at 5mg/kg once weekly for 2 weeks, then every 2 weeks untill 3 negative PCR or cultures were documented. ADV was first detected at a median of 53 days (range 6–319 days) after HSCT. The most common clinical manifestations were diarrhea (53%), fever (21%), hemorrhagic cystitis (12%), and pneumonitis (11%). Fourteen (25%) patients were asymptomatic and four (7%) patients had exacerbation of an ongoing GVHD. The virus was isolated from stool 53%, blood 50%, urine 16%, respiratory specimens 16% and the cerebrospinal fluid in 1 patient. Twenty (35%) patients had the virus isolated from more than 2 sites. Of the 30 patients who initially had ADV only in stool, 77% of them became PCR-positive in the blood while on CDV therapy, at a median of 10 days after ADV was first detected from the stool. The median duration of therapy was 60 days (range 1–270), with a median of 5 doses given (range 1–22). CDV treatment was associated with resolution of diarrhea, hemorrhagic cystitis, fever and pneumonitis in 56 patients in whom the virus became undetectable by both cultures and quantitative PCR. There was one adenovirus-related death due to pneumonitis and ARDS. No cases of dose-limiting nephrotoxicity were observed. Cidofovir was demonstrated to be safe and effective for the treatment of ADV infection in this predominantly pediatric HSCT patient population. Vigilant surveillance for ADV and early treatment with CDV can prevent the poor outcomes associated with ADV disease. A larger prospective study will be needed to further determine the role of CDV in the treatment of ADV in patients after HSCT.