Epstein-Barr virus-associated lymphoproliferative disorder developed after anti-thymocyte globulin therapy in a patient with bone marrow failure associated with T-cell large granular lymphocytic leukemia.

A 75-year-old man was referred to our hospital for marked neutropenia and anemia. Bone marrow examination showed marked hypoplasia with 45.2% infiltration of CD3+, CD8+, CD16+ and CD57+ granular lymphocytes. Monoclonal rearrangement of T-cell receptor gene was observed by Southern blot analysis. Taking these findings together, T-cell large granular lymphocyte leukemia (T-LGL) with bone marrow failure was diagnosed. The patient was treated with immunosuppressive therapy (IST) consisting of anti-thymocyte globulin and cyclosporine. Although pancytopenia subsided after IST, fever and lymphoadenopathy developed on the 29th day after IST. The presence of Epstein-Barr virus (EBV) in peripheral blood was confirmed using real time PCR (3.5×10(6) copies/10(6)WBC). Although gancyclovir and foscarnet were started, rapidly progressive hepatomegaly and liver dysfunction developed. The patient died on the 42nd day after IST. Autopsy specimen showed infiltration of abnormal CD20-positive large lymphocytes in the portal area of the liver, white pulp of the spleen, kidneys and adrenal glands. The nuclear EBV-encoded RNA (EBER) stain was positive in the abnormal large lymphocytes and a diagnosis of EBV-associated B-cell lymphoproliferative disorder (EBV-LPD) was made. We should regard the potential risk of EBV-LPD after immunosuppressive therapy for patients with bone marrow failure caused by T-LGL.