Divergent CMV and EBV co-infection impact in adult and pediatric hematopoietic stem cell transplantation recipients.
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BACKGROUND: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivations are major complications after hematopoietic stem cell transplantation (HCT), but co-infection epidemiology and outcomes in combined adult-pediatric cohorts remain poorly defined. MATERIALS AND METHODS: This retrospective single-center study analyzed 941 consecutive HCT recipients (2015-2023). CMV and EBV were quantified by whole-blood qPCR (positivity ≥153 and ≥433 copies/mL, respectively). CMV testing was weekly until day +100 post-HSCT; EBV testing followed clinical indication at the treating physician's discretion. IgG serostatus is not routinely tested at KHCC for post-transplant monitoring. Acknowledging some missing values, we evaluated the incidence, risk factors, and survival impact of CMV/EBV co-infection using chi-square tests, Kaplan-Meier analysis, and multivariable logistic and Cox proportional-hazards regression. RESULTS: Among 941 recipients (56.5% adult, 43.5% pediatric), adults received 89.1% of CMV tests (838/941) and 76.6% of CMV infections (105/137), whereas pediatric patients accounted for 59.8% of EBV infections (76/127); EBV testing covered 65.5% (616/941). Co-infection incidence was 7.6% (70/916). Co-infection was significantly associated with allogeneic transplant (p=0.004), haploidentical donor (p=0.010), reduced-intensity conditioning (p=0.017), and acute graft-versus-host disease (aGVHD) (p=0.028), but not with malignancy status (54/70 [77.1%] vs. 577/760 [75.9%] malignant; p=0.819); haploidentical (vs. related) donor type remained independent on multivariable analysis (adjusted OR 2.01, 95% CI 1.18-3.41, p=0.0098). CMV monoinfection was associated with adult age and haploidentical transplantation; EBV monoinfection with pediatric age, non-malignant disease, and aGVHD. Pediatric 3-year overall survival (OS) was superior (78.4% vs. 64.6%; median follow-up 41.8 months). The difference in 3-year OS between co-infected (67.3%) and non-co-infected (70.9%) patients did not reach statistical significance (Kaplan-Meier log-rank p = 0.4046; crude mortality by Pearson chi-square, p = 0.286); chronic GVHD was the only independent predictor of OS (adjusted HR 0.016, 95% CI 0.002-0.150, p=0.0003). CONCLUSION: CMV and EBV post-HCT exhibit distinct, age-associated risk profiles, and co-infection defines a high-risk phenotype linked to intensive immunosuppression and aGVHD. Three-year OS did not differ significantly between groups; given the observational design, selection bias from non-uniform EBV testing, and possible type II error, this should not be taken as evidence that pre-emptive strategies eliminate the survival impact of co-infection. Findings support age- and risk-adapted viral monitoring.