Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis subsequent to rabbit antithymocyte globulin administration and successfully treated with rituximab in a patient with aplastic anemia

Abstract

Rabbit antithymocyte globulin (ATG) is an effective immunosuppressive therapy for patients with aplastic anemia (AA). However, Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) is a rare but serious complication of the therapy. An 81-year-old man was diagnosed with severe AA on the occasion of melena. Because cyclosporine monotherapy did not improve his condition, rabbit ATG was additionally administered. Thirty-one days after the administration of rabbit ATG, the patient presented with fever and general malaise. His liver and renal function tests showed rapid decline, and the patient went into shock. Although atypical lymphocytes in the peripheral blood, hepatosplenomegaly, and lymphadenopathy were not detected, the peripheral blood EBV-DNA load and serum ferritin levels were high, and his bone marrow aspiration specimen revealed hemophagocytic findings, leading to a diagnosis of EBV-LPD. He was treated with rituximab and recovered immediately. A total of 480 days have passed since the patient was administered the rabbit ATG, and he remains in AA remission without EBV-LPD relapse. This case suggests that rituximab is an effective therapy for EBV-LPD manifesting as EBV-associated hemophagocytic lymphohistiocytosis and indicates that monitoring the EBV-DNA load contributes to the diagnosis.