Adenovirus infection in allogeneic hematopoietic cell transplantation

Abstract Adenovirus (AdV) infection occurs in 0–20% of patients in the first 3–4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than in adult patients. About 50% of AdV infections involve the blood, which in turn, correlates with an increased risk developing AdV diseases, end‐organ damage, and 6‐month overall mortality. The main risk factors for AdV infection are T‐cell depletion of the graft by ex vivo selection procedures or in vivo use of alemtuzumab or antithymocyte serum, development of graft versus host disease (GVHD) grade III–IV, donor type (haploidentical or human leucocyte antigen mismatched related donor > cord blood> unrelated matched donor) and severe lymphopenia (<0.2 × 10 9 /L). The prevention of AdV disease relies on early diagnosis of increasing viral replication in blood or stool and the pre‐emptive start of cidofovir as viral load exceeds the threshold of ≥10 2–3 copies/mL in blood and/or 10 6 copies/g stool in the stool. Cidofovir (CDV), a cytosine monophosphate nucleotide analog, is currently the only antiviral recommended for AdV infection despite limited efficacy and moderate risk of nephrotoxicity. Brincidofovir, a lipid derivative of CDV with more favorable pharmacokinetics properties and superior efficacy, is not available and currently is being investigated for other viral infections. The enhancement of virus‐specific T‐cell immunity in the first few months post‐HCT by the administration of donor‐derived or third‐party‐donor‐derived virus‐specific T‐cells represents an innovative and promising modality of intervention and data of efficacy and safety of the ongoing prospective randomized studies are eagerly awaited.