Management of adenovirus in children after allogeneic hematopoietic stem cell transplantation

Abstract

Adenovirus (ADV) can cause significant morbidity and mortality in children following haematopoietic stem cell transplantation (HSCT), with an incidence of up to 27% and notable associated morbidity and mortality. T-cell depleted grafts and severe lymphopenia are major risk factors for the development of adenovirus disease after HSCT. Current antiviral treatments are at best virostatic and may have significant side effects. Adoptive transfer of donor-derived virus-specific T cells has been shown to be an effective strategy for the prevention and treatment of ADV infection after HSCT. Here we review progress in the field and present a pathway for the management of adenovirus in the posttransplant setting.

Figure 1

Structure of adenovirus.

Figure 2

Algorithm for the management of ADV reactivation in children after allogeneic stem cell transplantation.

Figure 3

Protocols for generating virus-specific T cells. (a) Donor identified as ADV responder by IFN-γ secretion assay (Miltenyi Biotec, Bergisch Gladbach, Germany). Peripheral blood mononuclear cells (PBMC) isolated and incubated overnight with ADV Hexon protein. Responding cells captured with IFN-γ reagent, anti-IFN-γ microbead and magnetically enriched with CliniMACS (Miltenyi Biotec) [60]. (b) Donor PBMC incubated over 10 days with ADV5 hexon peptide and cytokines. Expanded cells isolated and infused into patients after QA/QC testing [61]. (c) EBV-transformed B cell lines (EBV-LCLs) generated from donor PBMCs by infecting with EBV virus. Donor PBMCs are transfected with Ad5f35pp65 vector (replication-competent adenovirus-negative) and later restimulated several times by EBV-LCLs that have been transduced with the same vector [62].