Blinatumomab exposure prior to allogeneic stem cell transplantation is associated with increased Epstein-Barr virus reactivation

Blinatumomab, a CD19/CD3 bispecific T-cell engager, is frequently used for B-cell acute lymphoblastic leukemia (B-ALL) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although its efficacy in achieving measurable residual disease negativity is well established, its profound B-cell depletion and potential immunomodulatory effects may exacerbate post-transplant viral reactivation risks, particularly in the context of the inherent immunosuppression associated with allo-HSCT. In this matched retrospective cohort study, we identified 97 consecutive B-ALL patients who received blinatumomab prior to allo-HSCT between January 2021 and December 2024. Using 1:2 propensity score matching based on gender, age, and pre-transplant chemotherapy regimen, we selected 194 control patients from the same period who underwent allo-HSCT without prior blinatumomab exposure. Clinical outcomes were compared between the two cohorts. By day 100, EBV viremia incidence was significantly higher in the blinatumomab group (41.5% vs. 26.4%, p = 0.009), with blinatumomab identified as an independent risk factor (HR = 1.792, 95% CI 1.206–2.661, p = 0.004). Notably, immunoglobulin analysis revealed markedly lower IgA levels in the blinatumomab group (0.298 vs. 0.544 g/L, p < 0.001), while T-cell (CD3+/CD4+/CD8+) and B-cell (CD19+) reconstitution did not differ. One-year overall survival (OS) and non-relapse mortality (NRM) were also comparable. Blinatumomab exposure is associated with increased EBV reactivation post-allo-HSCT, likely linked to humoral immunity impairment. These findings underscore the need for enhanced EBV monitoring in this population after allo-HSCT.