Two Cases of Chronic Active Epstein-Barr Virus Infection (CAEBV) Successfully Treated with Allogeneic Bone Marrow Transplantation and Induction of Specific Cytotoxic T Lymphocyte (CTL).

Chronic active Epstein-Barr virus infection (CAEBV) is a heterogenous EBV-related disorder, characterized by clonal expansion of EBV-infected T or NK cells. Although CAEBV is a high mortality and morbidity disease with life-threatening complications, effective treatment regimens have not yet been established. The pathogenesis and etiology of CAEBV are not well characterized. The clonal expansion of EBV-associated T or NK cells has been suggested to play important roles in the pathogenesis of CAEBV. It is not clear why EBV-associated abnormal cells cannot be excluded, because of a factor on the virus side or a function on the host side. We report two cases of CAEBV in which allogeneic bone marrow transplantation (BMT) was performed soon after diagnosis. After BMT, the EBV genome titer decreased as cytotoxic T lymphocyte (CTL) activity gradually increased.

Case 1: A five-year-old boy had exhibited prolonged fever, lymphadenopathy, and severe liver dysfunction for more than 6 months. Clonally proliferating EBV-infected T cells and abnormally high titers of EBV-related antibodies were detected. No EBV-specific CTLs were detected. The patient was given a diagnosis of T-cell type CAEBV and he received BMT (the donor was his 1-locus mismatched mother) 6 months after diagnosis. Severe treatment-related toxicity did not occur. After BMT, the EBV genome titer gradually decreased as the CTL activity increased. At 2 months after BMT, the EBV genome titer of the patient was nearly negative.

Case 2: A two-year-old girl had exhibited a persistent fever of unknown etiology and hepatosplenomegaly. Abnormally high titers of EBV-related antibodies were detected and NK cells in her peripheral blood contained a high EBV genome titer. The EBV-specific CTL levels were low. She received BMT from an unrelated donor 3 months after diagnosis. Toxicity other than grade 2 graft-versus-host disease was not detected. After BMT, the EBV genome titers decreased gradually as the CTL activity increased.

Conclusion: These cases suggest that not only high-dose chemotherapy as a preconditioning treatment of BMT, but also that increased CTL activity to eliminate virus-infected cells might be effective. Additional cases should be studied to establish effective treatments.