title: Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States.
abstract: Chronic active EBV disease (CAEBV) is a lymphoproliferative disorder characterized by markedly elevated levels of antibody to EBV or EBV DNA in the blood and EBV RNA or protein in lymphocytes in tissues. We present our experience with CAEBV during the last 28 years, including the first 8 cases treated with hematopoietic stem cell transplantation in the United States. Most cases of CAEBV have been reported from Japan. Unlike CAEBV in Japan, where EBV is nearly always found in T or natural killer (NK) cells in tissues, EBV was usually detected in B cells in tissues from our patients. Most patients presented with lymphadenopathy and splenomegaly; fever, hepatitis, and pancytopenia were common. Most patients died of infection or progressive lymphoproliferation. Unlike cases reported from Japan, our patients often showed a progressive loss of B cells and hypogammaglobulinemia. Although patients with CAEBV from Japan have normal or increased numbers of NK cells, many of our patients had reduced NK-cell numbers. Although immunosuppressive agents, rituximab, autologous cytotoxic T cells, or cytotoxic chemotherapy often resulted in short-term remissions, they were not curative. Hematopoietic stem cell transplantation was often curative for CAEBV, even in patients with active lymphoproliferative disease that was unresponsive to chemotherapy. These studies are registered at http://www.clinicaltrials.gov as NCT00032513 for CAEBV, NCT00062868 and NCT00058812 for EBV-specific T-cell studies, and NCT00578539 for the hematopoietic stem cell transplantation protocol.
authors: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA. jcohen@niaid.nih.gov
authors: Jeffrey I
authors: JI
authors: Cohen
authors: Elaine S
authors: ES
authors: Jaffe
authors: Janet K
authors: JK
authors: Dale
authors: Stefania
authors: S
authors: Pittaluga
authors: Helen E
authors: HE
authors: Heslop
authors: Cliona M
authors: CM
authors: Rooney
authors: Stephen
authors: S
authors: Gottschalk
authors: Catherine M
authors: CM
authors: Bollard
authors: V Koneti
authors: VK
authors: Rao
authors: Adriana
authors: A
authors: Marques
authors: Peter D
authors: PD
authors: Burbelo
authors: Siu-Ping
authors: SP
authors: Turk
authors: Rachael
authors: R
authors: Fulton
authors: Alan S
authors: AS
authors: Wayne
authors: Richard F
authors: RF
authors: Little
authors: Mitchell S
authors: MS
authors: Cairo
authors: Nader K
authors: NK
authors: El-Mallawany
authors: Daniel
authors: D
authors: Fowler
authors: Claude
authors: C
authors: Sportes
authors: Michael R
authors: MR
authors: Bishop
authors: Wyndham
authors: W
authors: Wilson
authors: Stephen E
authors: SE
authors: Straus
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007564:Japan; D007694:Killer Cells, Natural / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D015996:Survival Rate; D013601:T-Lymphocytes / Q000473:pathology; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D012367:RNA, Viral