In July 2021, a study led by Professor Zhengzheng Fu from the First Affiliated Hospital of Soochow University was published in the international academic journal ——Annals of Hematology. The title of the study is “Time-Dependent Effects of Early-Onset Epstein-Barr Viremia on Adult Acute Leukemia Patients Following Allo-HSCT with ATG-Containing MAC Regimen“. This study concludes with a call for further research into the mechanisms driving early-onset EBV reactivation and its long-term effects on transplant outcomes.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a cornerstone in the treatment of a wide range of hematologic malignancies, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). This procedure involves the administration of conditioning regimens to ablate the patient’s bone marrow, facilitating the engraftment of donor stem cells. The inclusion of anti-thymocyte globulin (ATG) in myeloablative conditioning (MAC) regimens has significantly improved transplant outcomes by reducing the incidence and severity of graft-versus-host disease (GVHD). However, the intensified immunosuppression required for GVHD prophylaxis raises the vulnerability to opportunistic infections and complications, notably the reactivation of latent viruses such as Epstein-Barr virus (EBV).
EBV reactivation post-transplant can manifest a spectrum of clinical presentations, from asymptomatic viremia to the potentially lethal EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD). Early-onset EBV viremia, defined as occurring within 100 days post-transplant, is particularly concerning due to its association with increased mortality rates. Despite its significance, the temporal dynamics of EBV viremia’s impact on transplant outcomes remain poorly understood. This study aims to shed light on these dynamics by exploring the time-dependent effects of early-onset EBV viremia on adult acute leukemia patients who have undergone allo-HSCT with an ATG-containing MAC regimen.
This retrospective cohort study includes 296 patients diagnosed with acute leukemia who underwent allo-HSCT with an ATG-containing MAC regimen between January 2013 and December 2015. The study cohort comprises a diverse patient population, including recipients of unrelated donor HSCT (URD-HSCT) and haploidentical donor HSCT (HID-HSCT), to ensure the findings are broadly applicable. High-resolution DNA typing techniques were employed for donor-recipient HLA matching, and EBV-DNA load in peripheral blood was monitored as the primary indicator of EBV reactivation. Patients were classified based on the development of early-onset EBV viremia, and their outcomes were analyzed to ascertain the impact of this early reactivation on survival and transplant-related mortality.
The results section has been enriched with detailed statistical analyses, including subgroup analyses examining the influence of donor type, GVHD incidence, and underlying leukemia subtype on the association between early-onset EBV viremia and transplant outcomes. Kaplan-Meier survival curves illustrate the differential impact of early-onset viremia on overall and event-free survival over time, highlighting a critical period in the first few months post-transplant where EBV viremia poses a heightened risk.
The article concludes with a call for further research into the mechanisms driving early-onset EBV reactivation and its long-term effects on transplant outcomes. It suggests areas for future investigation, such as prospective studies to validate these findings and explore the efficacy of different preemptive treatment strategies. The potential for refining risk stratification models to include the timing of EBV viremia as a prognostic factor is highlighted, underscoring the study’s contribution to improving patient management and outcomes in allo-HSCT.
This study illuminates the complex, time-dependent effects of early-onset EBV viremia on transplant outcomes in patients with acute leukemia. By demonstrating a significant impact on survival and transplant-related mortality within specific post-transplant windows, it underscores the importance of timely and targeted monitoring and intervention. These findings offer a valuable foundation for future research and clinical strategies aimed at mitigating the risks associated with EBV reactivation, ultimately enhancing the success of allo-HSCT for acute leukemia.
