血液系统恶性肿瘤异基因造血干细胞移植后的免疫重建与病毒再激活

To evaluate associations between post-transplant immune reconstitution, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) DNAemia/reactivation, and survival after allogeneic hematopoietic stem cell transplantation (HSCT).

We conducted a retrospective observational cohort study of 312 patients with hematologic malignancies who underwent allogeneic HSCT between 2016 and 2024. Bone marrow B-cell proportion and peripheral blood lymphocyte subsets were assessed longitudinally by flow cytometry. EBV and CMV reactivation was monitored by quantitative PCR and analyzed as surveillance-defined reactivation status. Landmark-based logistic regression evaluated associations between immune-reconstitution parameters and viral reactivation; receiver operating characteristic analysis assessed model discrimination, and Cox regression evaluated overall survival determinants.

CMV and EBV DNAemia/reactivation occurred in 42.0% and 31.4% of patients, respectively, and were significantly correlated ( = 0.191, p = 0.028). Higher bone marrow B-cell proportion at sixmonths was associated with lower odds of CMV DNAemia/reactivation (OR = 0.947, 95% CI: 0.901-0.995, p = 0.034). For EBV, an exploratory interaction between 12-month CD8 T-cell recovery and chronic GVHD was associated with EBV DNAemia/reactivation status ( p = 0.039). Lower NK-cell levels were observed in patients with EBV and CMV coinfection ( p = 0.021 and p = 0.036, respectively). Overall survival was mainly associated with relapse (HR = 5.5, p 0.001) and conditioning regimen, whereas viral reactivation was not significantly associated with survival. DISCUSSION: Intermediate immune-reconstitution landmarks showed distinct associations with surveillance-defined viral reactivation, particularly six-month B-cell proportion for CMV and CD8 T-cell recovery in the context of chronic GVHD for EBV.

Longitudinal immune-reconstitution patterns may help characterize persistent post-HSCT immune vulnerability, although prospective studies incorporating viral timing and treatment-exposure data are needed for validation.