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Efficacy of Brincidofovir in Pediatric Stem Cell Transplant Recipients With Adenovirus Infections.

BACKGROUND
Adenovirus (AdV) infections are of particular concern in pediatric hematopoietic stem cell transplantation (HSCT) recipients as therapeutic options are limited. Brincidofovir (BCV) is the lipid-conjugated pro-drug of cidofovir (CDV) with oral bioavailability and higher intracellular concentrations of the active drug.


METHODS
In this retrospective, single-center analysis, we included allogeneic pediatric HSCT recipients with refractory AdV infections because of contraindications or insufficient response to CDV. Common posttransplant viruses were monitored at least weekly by PCR in blood, stool, and urine.


RESULTS
Each of the 8 patients received 6 to 12 doses of BCV. BCV treatment was initiated between days +5 and +77. AdV DNAemia and intestinal AdV infection disappeared completely in 6/8 patients. Early AdV DNAemia before day +21 did not result in increased mortality. One patient with a systemic, acyclovir-resistant HSV-1 infection responded rapidly to BCV. Four patients did not survive. AdV infection-related death in 2 patients was accompanied by >1 × 109/mL AdV copy numbers in the blood. Two more patients died of graft-vs-host disease and acute respiratory distress syndrome, respectively, both not related to AdV.


CONCLUSIONS
AdV DNAemia and intestinal infection subsided completely in 75% of pediatric HSCT recipients treated with BCV. AdV DNAemia exceeding 1 × 109/mL and a poor lymphocyte recovery of <250/µL were associated with high mortality. Early AdV DNAemia before day +21, however, did not result in a worse outcome. Although access to BCV is currently suspended, further clinical trials are needed to clarify the role of BCV in HSCT recipients with AdV infections and its potential benefit in preventing AdV DNAemia in immunocompromised patients.