Chronic active Epstein–Barr virus (CAEBV) infection is a rare and highly lethal lymphoproliferative disorder. The pathological basis of this condition involves Epstein–Barr virus (EBV) persisting in hematopoietic stem cells, driving clonal expansion of T cells or natural killer (NK) cells, and subsequently triggering systemic inflammatory responses and multi-organ failure. Current treatment modalities, encompassing antiviral medications, immunosuppressants, and cytotoxic chemotherapy, offer only transient remissions, with the majority of patients ultimately experiencing relapse. Recent single-cell sequencing and chimera studies have confirmed that EBV-infected hematopoietic stem cells constitute the “seed” cell population for CAEBV initiation and maintenance. This finding indicates that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment known to date that can fully eradicate viral reservoirs and restore normal immunity, suggesting that it may represent a curative strategy. Nevertheless, transplantation timing, donor matching, conditioning intensity, and transplant-related complications have been shown to have a significant impact on long-term prognosis. The clinical decision-making process necessitates a high degree of individualization, incorporating molecular risk factors, disease activity, and comorbidities. Advancing research into the latent-lytic cycle regulation mechanisms of EBV, in addition to the clinical translation of small-molecule inhibitors targeting viral proteins and EBV-specific adoptive cell therapies, holds great promise for the future. One such potential avenue for future research is the development of an integrated “pre-transplant viral load reduction-post-transplant relapse prevention” strategy. This approach shows great potential in reducing transplant-related mortality and continuously improving survival outcomes for CAEBV patients.
Wang et al. (Thu,) studied this question.