The Impact of Cytomegalovirus Reactivation on Cytomegalovirus-Specific Immune Reconstitution in Hematopoietic Stem Cell Transplant Recipients Receiving Letermovir Prophylaxis

作者：C H Jiang, Lilan Jin, Luxiang Wang, Yanying Gu, Xiaoxia Hu, Gang Cai · 发表于：Open Forum Infectious Diseases · 年份：2026 · DOI：10.1093/ofid/ofag160 · 研究领域：Cytomegalovirus and herpesvirus research、Hematopoietic Stem Cell Transplantation、Viral-associated cancers and disorders

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 noninfectious CMV DNA. Based on DNase treatment results, patients were divided into 3 groups: (1) negative DNAemia (ND, n = 25): with no detectable CMV DNA; (2) DNase I-sensitive DNAemia (DSD, n = 26): with only DNase I-sensitive CMV DNA detected; (3) DNase I-resistant DNAemia (DRD, n = 25): with at least one episode of DNase I-resistant CMV DNAemia within 100 days posttransplant. CMV-specific T-cell responses were evaluated by multiparameter flow cytometry, and cytokine polyfunctionality was quantified using Combinatorial Polyfunctionality Analysis of Antigen-Specific T-cell Subsets analysis. Results Early CMV reactivation was associated with stronger CD8+ than CD4+ T-cell responses. DNase I–resistant DNAemia 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 re...