BACKGROUND: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a common alternative for patients with hematological malignancies. Epstein-Barr virus (EBV) reactivation is a common complication post-transplantation, but its impact on immune reconstitution and survival remains unclear.

OBJECTIVE: To compare immune reconstitution and survival between patients with and without EBV reactivation after haplo-HSCT.

DESIGN: A retrospective study was conducted involving 322 patients aged 18-60 years, diagnosed with hematological malignancies, who underwent haplo-HSCT at our center from January 2018 to December 2021.

METHODS: Data analysis was performed using SPSS (version 24.0) and R4.3.0 software. Statistical methods included Chi-square tests for qualitative variables, independent t tests for continuous variables, Kaplan-Meier method for survival analysis, and logistic regression for risk factor analysis.

RESULTS: After a median of 58 days posttransplant, 176 patients (54.6%) had EBV reactivation, but only 5 patients developed posttransplant lymphoproliferative disorder. Logistics multivariate analysis showed EBV IgA-negative donor, cytomegalovirus (CMV) reactivation, and graft-versus-host disease (GVHD) prophylaxis with anti-thymocyte globulin (ATG) were independent risk factors of EBV reactivation. Then a risk factor prediction model for EBV reactivation after transplantation was established based on the multivariate regression. The analysis based on the generalized linear mixed model showed dramatic improvements in the reconstitution of CD8⁺CD45RO⁺ memory T-cells and CD16⁺CD56⁺ NK cells of the EBV-reactivated group. There was no statistical difference in overall survival (p = 0.26), relapse-free survival (p = 0.72), GVHD-relapse free survival (p = 0.44), cumulative incidence of relapse (Gray's test p = 0.72), and transplant-related mortality (Gray's test p = 0.066) between patients with and without EBV reactivation.

CONCLUSION: Our study showed EBV IgA-negative donor, CMV reactivation, and GVHD prophylaxis with ATG were independent risk factors of EBV reactivation. Posttransplant EBV reactivation had no significant influence on the outcomes of patients, but its impact on immune reconstitution might be complicated. The predictive model based on the study could direct our attention toward patients at high risk of EBV reactivation.