Abstract
The ability to distinguish allogeneic hematopoietic cell transplant (allo-HCT) recipients at risk for cytomegalovirus (CMV) reactivation from those who are not is central for optimal CMV management strategies. Interferon γ (IFN-γ) produced by CMV-challenged T cells may serve as an immune marker differentiating these 2 populations. We prospectively monitored 63 CMV-seropositive allo-HCT recipients with a CMV-specific enzyme-linked immunospot (ELISPOT) assay and for CMV infection from the period before transplantation to day 100 after transplantation. Assay results above certain thresholds (50 spots per 250 000 cells for immediate early 1 or 100 spots per 250 000 cells for phosphoprotein 65) identified patients who were protected against CMV infection as long as they had no graft-versus-host disease and/or were not receiving systemic corticosteroids. Based on the multivariable Cox proportional hazards regression model, the only significant factor for preventing CMV reactivation was a CMV-specific ELISPOT response above the determined thresholds (adjusted hazard ratio, 0.21; 95% confidence interval, .05–.97; P = .046). Use of this assay as an additional tool for managing allo-HCT recipients at risk for CMV reactivation needs further validation in future studies. Application of this new approach may reduce the duration and intensity of CMV monitoring and the duration of prophylaxis or treatment with antiviral agents in those who have achieved CMV-specific immune reconstitution.
Highlights
In immunocompromised hosts, the production and replication of CMV may lead to infection and a variety of end-organ
This study is a proof-of-concept study to assess the ability of the CMV-specific enzyme-linked immunospot (ELISPOT) assay to identify CMV-seropositive allo-hematopoietic cell transplant. a Dose (HCT) recipients who have achieved immune reconstitution and so are not at risk for CMV reactivation
Sixty-three patients with hematologic malignancies and CMV seropositivity were enrolled in this study and monitored for 100 days after allo-HCT
Summary
The production and replication of CMV may lead to infection and a variety of end-organ. A new enzyme-linked immunospot (ELISPOT)–based assay (T-SPOT.CMV assay; Oxford Immunotec, Oxfordshire, United Kingdom) measures IFN-γ levels in peripheral blood mononuclear cells and has recently become commercially available in the United States and Europe. It allows the assessment of T-cell immune activity by detecting the production of IFN-γ following ex vivo stimulation with CMV antigens (immediate early 1 [IE-1] and phosphoprotein 65 [ pp65]); the peptides are designed to target both CD4+ and CD8+ T cells. This study is a proof-of-concept study to assess the ability of the CMV-specific ELISPOT assay to identify CMV-seropositive allo-HCT recipients who have achieved immune reconstitution and so are not at risk for CMV reactivation
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