Practice patterns and incidence of adenovirus infection in allogeneic hematopoietic cell transplant recipients: Multicenter survey of transplant centers in the United States

Abstract

Background Adenovirus (AdV) is increasingly recognized as a threat to successful outcomes after allogeneic hematopoietic cell transplantation (allo‐HCT). Guidelines have been developed to inform AdV screening and treatment practices, but the extent to which they are followed in clinical practice in the United States is still unknown. The incidence of AdV in the United States is also not well documented. The main objectives of the AdVance US study were thus to characterize current AdV screening and treatment practices in the United States and to estimate the incidence of AdV infection in allo‐HCT recipients across multiple pediatric and adult transplant centers. Methods Fifteen pediatric centers and 6 adult centers completed a practice patterns survey, and 15 pediatric centers and four adult centers completed an incidence survey. Results The practice patterns survey results confirm that pediatric transplant centers are more likely than adult centers to routinely screen for AdV, and are also more likely to have a preemptive AdV treatment approach compared to adult centers. Perceived risk of AdV infection is a determining factor for whether routine screening and preemptive treatment are implemented. Most pediatric centers screen higher‐risk patients for AdV weekly, in blood, and have a preemptive AdV treatment approach. The incidence survey results show that from 2015 to 2017, a total of 1230 patients underwent an allo‐HCT at the 15 pediatric transplant centers, and 1815 patients underwent an allo‐HCT at the 4 adult transplant centers. The incidences of AdV infection, AdV viremia, and AdV viremia ≥ 1000 copies/mL within 6 months after the first allo‐HCT were 23%, 16%, and 9%, respectively, for patients at pediatric centers, and 5%, 3%, and 2%, respectively, for patients at adult centers. Conclusions These findings provide a more recent estimate of the incidence of AdV infection in the United States, as well as a multicenter view of practice patterns around AdV infection screening and intervention criteria, in pediatric and adult allo‐HCT recipients.

Fulminant Adenoviral-Induced Hepatitis in Immunosuppressed Patients

“…As incidence is low, there is no defined treatment regimen for a HAdV hepatitis [ 1 , 4 , 23 ]. Published guidelines focus on treatment recommendations for patients following SCT [ 5 , 6 , 9 , 16 , 23 ]. Accordingly, immunosuppression should be reduced as T-cell recovery contributes to viral clearance [ 4 , 5 , 8 , 9 , 16 , 23 ].…”

“…Published guidelines focus on treatment recommendations for patients following SCT [ 5 , 6 , 9 , 16 , 23 ]. Accordingly, immunosuppression should be reduced as T-cell recovery contributes to viral clearance [ 4 , 5 , 8 , 9 , 16 , 23 ]. Patients 1 and 2 did not have immunosuppression when viremia evolved, or they were on local budesonide.…”

“…In addition to reducing immunosuppression, most data are available for the antiviral agent cidofovir [ 5 , 6 , 16 ]. However, its use is controversial [ 9 ].…”

“…These typically include stem-cell transplantation (SCT), solid-organ transplantation, human immunodeficiency virus (HIV) infection, or chemotherapy. In particular, post-allogenic SCT patients with graft-versus-host disease (GvHD), lymphopenia (absolute lymphocyte count <200/µL), use of anti-thymocyte globulin (ATG) or alemtuzumab therapy and T-cell-depleted grafts, or cord-blood administration are the most vulnerable populations [ 4 , 5 , 6 , 16 ]. Although these patients are at an increased risk, the diagnosis and the treatment of HAdV hepatitis are still challenging.…”

Detection of adenovirus hepatitis and acute liver failure in allogeneic hematopoietic stem cell transplant patients

“…The incidence of HAdV infection ranges between 2% and 15% in allo‐HSCT patients, in whom it manifests as cystitis, gastroenteritis, pneumonia, encephalitis, hepatitis, or disseminated systemic infection, and is frequently encountered after Herpes simplex virus and CMV 12‐16 . Previous reports have shown that the risk factors for post allo‐HSCT HAdV infection include GVHD of grade III or IV, detection of HAdV at two or more sites, T cell‐depleted grafts, unrelated donors, cord blood transplants, haplo transplants, Alemtuzumab, and ATG administration.…”