Adenovirus Infection in Pediatric Hematopoietic Cell Transplantation: A Challenge Still Open for Survival

Human Adenovirus (HAdV) infection occurs in 14-16% of patients in the early months after pediatric hematopoietic cell transplantation (HCT) and this correlates with a higher risk of developing HAdV disease and overall 6-month mortality. The main risk factors for HAdV infection are T-cell depletion of the graft by ex vivo CD34+ selection or in vivo use of alemtuzumab or anti-thymocyte serum, the development of grade III-IV graft versus host disease (GVHD), the type of donor (unrelated donor, cord blood, haploidentical, or HLA mismatched parent), and severe lymphopenia (<0.2 x 10(9)/L). The prevention of HAdV disease is based on early intervention with antivirals in the asymptomatic patient when the permitted viral load threshold in the blood (>= 10(2-3) copies/mL) and/or in the stool (10(9) copies/g stool) is exceeded. Cidofovir, a monophosphate nucleotide analog of cytosine, is the primary drug for preemptive therapy, used at 5 mg/kg/week for 2 weeks followed by 3-5 mg/kg every 2 weeks. The alternative schedule is 1 mg/kg every other day (three times/week). Enhancing virus-specific T-cell immunity in the first months post-HCT by donor-derived or third-party-derived virus-specific T cells represents an innovative and promising way of intervention, applicable both in prevention and therapeutic settings.

Automated summary

Human Adenovirus (HAdV) infection is common after pediatric hematopoietic cell transplantation, and the risk factors include T-cell depletion, GVHD, donor type, and severe lymphopenia. The prevention of HAdV disease includes early intervention with antivirals. Cidofovir is the primary drug for preemptive therapy. Enhancing virus-specific T-cell immunity is a promising intervention approach in the first months post-HCT.