ATG Plus Post-Transplantation Cyclophosphamide Improves EBV-DNA Clearance and GVHD in Patients of Adult Chronic Active Epstein-Barr Virus Disease Undergoing Allogeneic HSCT

Background: Chronic active Epstein-Barr virus disease (CAEBVD) faces a challenging prognosis due to its inflammatory and tumorigenic nature and lack of standard treatment. The outcomes of adults are more disheartening. We aim to elucidate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult CAEBVD, while clarifying whether the combination of antithymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) can improve survival and reduce transplant-related complications. Methods: We conducted a retrospective study analyzing adult CAEBVD patients who underwent allo-HSCT sequentially in the Department of Hematology at Tongji Hospital, Huazhong University of Science and Technology, from June 2015 to January 2022. Results: Of 20 patients included. The median age at diagnosis was 30.5 years, and the median follow-up time post-transplantation was 26.9 months. The 5-year overall survival (OS), progression-free survival (PFS), GVHD-free and relapse-free survival (GRFS), and non-relapse mortality (NRM) rates were 54.5%, 39.4%, 44.4%, and 37.4%, respectively. These data were similar in ATG alone (50.0%, 33.3%, 33.3%, and 40.0%) and ATG+PTCy (56.3%, 41.7%, 49.0%, and 37.5%). On multivariable Cox regression, pre-transplant hemophagocytic syndrome (25.0% vs. 75.0%, P =0.029) and higher EBV copies (25% vs. 61.9%, P =0.048) reduced the OS. On multivariable logistic regression, ATG+PTCy showed a lower incidence of grade II–IV acute GVHD (14.3% vs. 66.7%, P =0.037) and chronic GVHD (14.3% vs. 66.7%, P =0.037). Additionally, faster EBV clearance (P=0.002) and lower EBV reactivation ( P =0.018) were observed in ATG+PTCy. Conclusion: Allo-HSCT can facilitate long-term survival in approximately half of adult CAEBVD. ATG+PTCy regimen did not improve survival but demonstrated advantages over ATG alone in reducing GVHD, eliminating EBV, and decreasing EBV reactivation.