title: 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.
abstract: 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.
authors.affiliation: Department of Hematology, Nagano Red Cross Hospital, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sumi
authors.forename: Masahide
authors.initials: M
authors.lastname: Watanabe
authors.forename: Keijiro
authors.initials: K
authors.lastname: Sato
authors.forename: Ikuo
authors.initials: I
authors.lastname: Shimizu
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Ueki
authors.forename: Daigo
authors.initials: D
authors.lastname: Akahane
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ueno
authors.forename: Naoaki
authors.initials: N
authors.lastname: Ichikawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Asano
authors.forename: Hikaru
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000368:Aged; D000741:Anemia, Aplastic; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects*; D001853:Bone Marrow; D001855:Bone Marrow Diseases; D000080983:Bone Marrow Failure Disorders; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000209:etiology* / Q000821:virology*; D017809:Fatal Outcome; D006457:Hemoglobinuria, Paroxysmal / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D054066:Leukemia, Large Granular Lymphocytic / Q000150:complications*; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000821:virology*; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine