Timing of CMV-specific effector memory T cells predicts viral replication and survival after allogeneic hematopoietic stem cell transplantation

The aim of this study was to characterize timing, kinetic, and magnitude of CMV-specific immune response after hematopoietic stem cell transplantation (HSCT) and its ability to predict CMV replication and clinical outcomes. Using cell surface and intracellular cytokine staining by flow cytometry, CMV-specific T-cell response was measured in blood, while CMV viral load and chimerism were determined by real-time PCR. Patients that reconstituted CMV-specific T-cell response within 6weeks after Allo-SCT showed a more robust immune response (CD8(+): 0.7cells/l vs. 0.3/l; P-value=0.01), less incidence of CMV replication (33% vs. 89.5%; P-value=0.007), reduced viral loads (1.81 log copies/ml vs. 0 copies/ml; P-value=0.04), and better overall survival (72%; CI: 0.53-0.96 vs. 42% CI: 0.24-0.71; P-value=0.07) than patients with a delayed immune reconstitution. Viremic patients had significantly higher transplant-related mortality than nonviremic patients after 1year (33% CI: 0.15-0.52 vs. 0% CI: 0.05-0.34; P-value=0.01). Risk factors independently associated with viral replication were receptor pretransplant CMV-positive serostatus (P-value=0.02) and acquiring CMV-specific T-cell response after 6weeks post-transplantation (P-value=0.009). In conclusion, timing of acquiring a positive CMV-specific T-cell immune response after transplantation may identify patients with different risk for viral replication and different clinical outcomes, including survival.