Human cytomegalovirus (HCMV) infection, particularly when it is persistent, causes significant morbidity and mortality following allogenic stem cell transplantation (allo-SCT). While antiviral agents are the first-line therapy, they are limited by adverse events and acquired resistance. The authors were interested in the safety and efficacy of donor-derived HCMV-specific cytotoxic T cells (CTL) as a first-line therapy for HCMV infection after allo-SCT. They found that, in humanised HCMV-infected mice, first-line therapy with CTL does effectively treat systemic HCMV infection by promoting the restoration of graft-derived endogenous HCMV-specific immunity in vivo. When tested in a clinical trial, when compared with pair-matched high-risk controls, first-line therapy with CTL significantly reduced the rate of persistent (2.9% vs. 20.0%) and late (5.7% vs. 20.0%) HCMV infections. It also significantly reduced the cumulative incidence of persistent HCMV infection (hazard ratio [HR] 0.13, 95%CI 0.10-0.82), significantly lowered 1-year treatment-related mortality (HR 0.15, 95%CI 0.11-0.90) and improved 1-year overall survival (HR 6.35, 95%CI 1.05-9.00). In addition, first-line therapy with CTL was found to promote the quantitative and functional recovery of CTL in patients, which was associated with HCMV clearance. Therefore there are a number of benefits of using CTL together with antiviral drugs as a first-line therapy for treating HCMV infection, possibly by stimulating the recovery of endogenous HCMV-specific immunity.
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