Different graft-vs-host disease prophylaxis strategy for allogeneic hematopoietic stem cell transplantation in adults with chronic active EBV infection

Abstract

Abstract Background: Adult patients with chronic active Epstein-Barr virus (CAEBV) infection face a challenging prognosis. Increasing evidence shows that adult patients with CAEBV infections exhibit higher disease incidence and significantly poorer transplantation outcomes, characterized by faster progression and more aggressive disease. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative intervention，but the 3-year OS of adults was 31%, which was much lower than that for children (100%) and adolescents (57%) in some studies. However, most existing literature is outdated. While allo-HSCT theory and technology have advanced significantly over the past decade, it is crucial to determine whether these advancements have improved survival and transplantation outcomes for patients with CAEBV infection in adult haematology units. Furthermore, there is limited research into the impact of various GVHD prophylaxis strategies, such as post-transplant cyclophosphamide (PTCy), anti-thymocyte globulin (ATG), or a combination of the two, on post-transplant complications and prognosis in adult CAEBV patients. Methods: This study retrospectively reviewed patients receiving allo-HSCT at Tongji Hospital's Department of Hematology. Results: Of 20 patients included, 6 (33.3%) received anti-thymocyte globulin (ATG) as graft-vs-host disease (GVHD) prophylaxis strategy, 14 (66.7%) received combination of ATG and post-transplant cyclophosphamide (ATG+PTCy). Median age at diagnosis was 30.5 years, and 65% of patients were male; 55% received combination chemotherapy prior to transplantation. An HCT-CI score greater than 3 was observed in 35 % of patients. Hemophagocytic syndrome (HPS) was observed in 40% of patients prior to transplantation. The median follow-up from diagnosis to transplantation was 4.02 months, and 55% of patients received a haploidentical transplant. The median follow-up post-transplantation was 26.9 months. The 5-year overall survival (OS), progression-free survival (PFS), GVHD-free, relapse-free survival (GRFS), and non-relapse mortality (NRM) rates were 54.5%, 39.4%, 44.4%, and 37.4%, respectively. OS, PFS, GRFS, and NRM were similar regardless of GVHD prophylaxis strategy on multivariable Cox regression analysis. However, 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 Logistics regression analysis, 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. Conclusions: Allo-HSCT can facilitate long-term survival in approximately half of adult CAEBV patients,with the ATG+PTCy regimen demonstrating advantages in GVHD prophylaxis over ATG alone.