Abstract Background Cytomegalovirus (CMV) remains the most common viral infection after hematopoietic stem cell transplantation (HSCT).The clinical significance of different CMV DNA forms remains unclear, particularly regarding CMV-specific immune reconstitution. Methods A total of 76 HSCT recipients were enrolled. A quantitative DNase I–resistant CMV-DNA assay was performed to distinguish infectious from non-infectious CMV DNA. Based on DNase treatment results, patients were divided into three groups: (1) Negative DNAemia (ND, n = 25): with no detectable CMV DNA; (2) DNase-sensitive DNAemia (DSD, n = 26): with only DNase-sensitive CMV DNA detected; (3) DNase-resistant DNAemia (DRD, n = 25): with at least one episode of DNase-resistant CMV DNAemia within 100 days post-transplant. CMV-specific T-cell responses were evaluated by multiparameter flow cytometry, and cytokine polyfunctionality was quantified using COMPASS analysis. Results Early CMV reactivation was associated with stronger CD8+ than CD4+ T-cell responses. DRD patients exhibited significantly enhanced polyfunctional CD8+ T-cell responses compared with ND patients, while DSD patients did not. Among patients with detectable CMV DNA, stronger CD8+ T-cell responses correlated with higher peak viral loads and greater viral shedding. Elevated CMV-specific CD4+ T-cell responses were associated with higher peak CMV-DNA loads and reduced risk of CMV reactivation after day 100 post-transplant. In multivariable analysis, acute graft-versus-host disease (aGvHD) was an independent risk factor for CMV reactivation. Conclusions CMV-specific immune reconstitution appears delayed in DSD compared with DRD patients, potentially reflecting limited exposure to replication-competent virus. Assessment of CMV-specific T-cell polyfunctionality may help identify HSCT recipients at increased risk for late CMV reactivation.
Jiang et al. (Thu,) studied this question.