Early prophylactic rituximab reduces EBV infection and PTLD in high-risk patients receiving allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Epstein-Barr virus (EBV) infection is a major complication after allogeneic hematopoietic cell transplantation (allo-HCT) and may progress to post-transplant lymphoproliferative disorder (PTLD). Current management relies on preemptive rituximab guided by EBV DNA monitoring, but this approach is inherently dependent on detectable EBV DNAemia and may not prevent early viral expansion. OBJECTIVES: To evaluate the efficacy and safety of prophylactic rituximab compared with a standard preemptive strategy in preventing EBV infection and PTLD in high-risk patients receiving allo-HCT. STUDY DESIGN: In this multicenter retrospective cohort study, patients were stratified according to receipt of prophylactic rituximab (n = 280) or a preemptive rituximab strategy (n = 434). The primary endpoint was the 180-day cumulative incidence of EBV infection. Secondary endpoints included EBV-PTLD, transplant-related outcomes, immune reconstitution, and survival. To account for baseline imbalances, inverse probability of treatment weighting (IPTW) was applied. Additionally, Fine-Gray proportional subdistribution hazards model was utilized to identify independent risk and protective factors. RESULTS: Prophylactic rituximab was associated with a significantly lower 180-day incidence of EBV infection compared with the preemptive strategy (4.74% vs. 36.83%, P < 0.001), and a reduced incidence of PTLD (1.10% vs. 4.52%, P = 0.040). In multivariable analysis, prophylactic rituximab remained an independent protective factor for EBV infection (sHR = 0.12, P < 0.001). No significant differences were observed in overall survival, non-relapse mortality, relapse incidence, or major transplant-related complications. B-cell recovery remained suppressed through 12 months, whereas serum IgG levels and first-year IVIG use were comparable between groups. CONCLUSIONS: Prophylactic rituximab markedly reduces EBV infection and PTLD in high-risk patients undergoing allo-HCT, without adversely affecting survival or transplant outcomes. These findings support a risk-adapted prophylactic strategy for patients at high risk of EBV-related complications and warrant prospective evaluation of patient selection and long-term safety.