Work

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

Year: 2026

Type: article

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 reduced risk of CMV reactivation after day 100 posttransplant. In multivariable analysis, acute graft versus host disease was an independent risk factor for CMV reactivation. Conclusions Cytomegalovirus-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.

Source: Open Forum Infectious Diseases

DOI: 10.1093/ofid/ofag160

Authors: Cen Jiang, Lilan Jin, Luxiang Wang, Yanying Gu, Xiaoxia Hu, Gang Cai

Institutions: Shanghai Jiao Tong University, Ruijin Hospital, Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics

Language: English

Topic: Cytomegalovirus and herpesvirus research

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,053