A Clinical Algorithm Identifies High Risk Pediatric Oncology and Bone Marrow Transplant Patients Likely to Benefit From Treatment of Adenoviral Infection

Abstract

Background Adenoviral infections cause morbidity and mortality in blood and marrow transplantation and pediatric oncology patients. Cidofovir is active against adenovirus, but must be used judiciously because of its nephrotoxicity and unclear indications. Therefore, before introducing cidofovir use during an adenoviral outbreak, we developed a clinical algorithm to distinguish low risk patients from those who merited cidofovir therapy because of significant adenoviral disease and high risk for death. Objective This study was conducted to determine whether the algorithm accurately predicted severe adenovirus disease and whether selective cidofovir treatment was beneficial. Study Design A retrospective analysis of a pediatric oncology/ blood and marrow transplantation cohort prealgorithm and postalgorithm implementation was performed. Results Twenty patients with adenovirus infection were identified (14 high risk and 6 low risk). All low-risk patients cleared their infections without treatment. Before algorithm implementation, all untreated high-risk patients died, 4 out of 5 (80%), from adenoviral infection. In contrast, cidofovir reduced adenovirus-related mortality in the high-risk group postalgorithm implementation (9 patients treated, 1 patient died; RR 0.14, P<0.05) and all treated high-risk patients cleared their virus. Conclusions The clinical algorithm accurately identified patients at high risk for severe fatal adenoviral disease who would benefit from selective use of cidofovir.

Eradication of disseminated adenovirus infection in a pediatric hematopoietic stem cell transplantation recipient using the novel antiviral agent CMX001

“…Risk factors for disease include young age, allogeneic transplantation, T cell depleting conditioning regimens, unrelated or HLA-mismatched grafts, lymphocytopenia, and GvHD. 8,9 The expected mortality rate in patients with disseminated adenovirus disease is up to 80% depending on the organ system involved. 8 There are currently no FDA-approved therapies for adenovirus infection, with only anecdotal, off-label uses described for a variety of anti-viral agents or immune therapies such as IVIG or donorlymphocyte infusion.…”

Brincidofovir for Asymptomatic Adenovirus Viremia in Pediatric and Adult Allogeneic Hematopoietic Cell Transplant Recipients: A Randomized Placebo-Controlled Phase II Trial

“…The incidence of infection with adenoviruses in patients undergoing allogeneic HCT is estimated to be between 5% and 47% [4][5][6][7][8][9][10][11], with higher incidence in pediatric patients; most cases of serious disease occur in the first 100 days after transplantation [5,6,11]. Mortality rates of up to 26% are reported for untreated HCT recipients with symptomatic localized infection, and mortality rates of 80% or greater are reported for lower respiratory tract infections associated with disseminated disease [3,5,[10][11][12][13][14].…”

Risk Factors for Molecular Detection of Adenovirus in Pediatric Hematopoietic Stem Cell Transplantation Recipients

“…Multiple groups have attempted to identify specific risk factors for infection and/or disease to identify populations at greatest risk for poor outcome [16,17]. Published risk factors for AdV infection include younger age, GVHD, second HSCT, allogeneic transplantation, T cell depletion, unrelated or mismatched grafts, total body irradiation (TBI), lymphopenia, bone marrow as the stem cell source, and myelodysplastic syndrome as indications for transplantation [16,18].…”