Immune Reconstitution and Viral Reactivation - EMJ

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Immune Reconstitution and Viral Reactivation After HSCT

immune reconstitution

Key Summary:

  • Immune reconstitution was linked to CMV and EBV reactivation after allogeneic HSCT.
  • Six-month B-cell recovery was associated with lower CMV DNAemia/reactivation risk.
  • Immune monitoring may help identify persistent viral vulnerability after transplantation.

IMMUNE reconstitution after allogeneic haematopoietic stem cell transplantation (HSCT) was associated with distinct patterns of cytomegalovirus (CMV) and Epstein–Barr virus (EBV) DNAemia/reactivation, although viral reactivation was not significantly linked to overall survival.

Study Examines Immune Reconstitution

Researchers conducted a retrospective observational cohort study involving 312 patients with haematological malignancies who underwent allogeneic HSCT between 2016 and 2024. Bone marrow B-cell proportions and peripheral blood lymphocyte subsets were assessed longitudinally using flow cytometry.

CMV and EBV reactivation were monitored using quantitative polymerase chain reaction and analysed according to surveillance-defined reactivation status. Landmark-based logistic regression was used to examine relationships between immune-reconstitution measures and viral reactivation, while receiver operating characteristic analysis assessed model discrimination. Cox regression was used to investigate determinants of overall survival.

Immune Reconstitution Shows Distinct Associations

CMV DNAemia/reactivation occurred in 42.0% of patients, while EBV DNAemia/reactivation occurred in 31.4%. The two viral outcomes were significantly correlated (ρ=0.191; p=0.028).

Higher bone marrow B-cell proportions at 6 months were associated with lower odds of CMV DNAemia/reactivation (odds ratio: 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 graft-versus-host disease was associated with EBV DNAemia/reactivation status (p=0.039).

Lower natural killer (NK) cell levels were also observed among patients with EBV and CMV coinfection (p=0.021 and p=0.036, respectively).

Overall survival was primarily associated with relapse and conditioning regimen. Relapse was associated with substantially poorer survival, while viral reactivation itself was not significantly associated with overall survival.

Implications For Post-Transplant Monitoring

The findings suggest that immune reconstitution may provide clinically relevant markers of persistent immune vulnerability following allogeneic HSCT. In particular, 6-month B-cell recovery showed an association with CMV reactivation, while CD8⁺ T-cell recovery in the context of chronic graft-versus-host disease was associated with EBV reactivation status.

However, the researchers noted that prospective studies are needed to validate these observations and incorporate the timing of viral events and treatment exposures. Such studies could help clarify how longitudinal immune-reconstitution patterns relate to viral vulnerability after transplantation.

Reference

Qaiser M et al. Immune reconstitution and viral reactivation after allogeneic hematopoietic stem cell transplantation in hematologic malignancies. Hematology. 2026;31(1).

Featured image: Nawarat on Adobe Stock.

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