title: A case series of CAEBV of children and young adults treated with reduced-intensity conditioning and allogeneic bone marrow transplantation: a single-center study.
abstract: BACKGROUND
  Epstein-Barr virus (EBV)-infected T or NK cells cause chronic active EBV infection (CAEBV). Allogeneic hematopoietic stem cell transplantation (HSCT) is curative treatment for CAEBV patients. However, chemotherapy prior to HSCT and optimal conditioning regimen for allogeneic HSCT are still controversial.
  
  
  METHODS
  We retrospectively analyzed five patients with CAEBV treated with reduced-intensity conditioning (RIC) consisted of fludarabine, cyclophosphamide, and low-dose total-body irradiation followed by allogeneic bone marrow transplantation in a single institute. Only one of five patients received chemotherapy prior to transplantation. We analyzed EBV-infected cells in a patient whose EBV load increased after HSCT by T-cell repertoire assay, separation of T-cell subpopulations, in situ hybridization and microsatellite analysis.
  
  
  RESULTS
  All five patients achieved engraftment, complete chimera, and eradication of EBV load. All patients have been alive without any serious regimen-related toxicity for more than 16 months following HSCT. However, one patient transplanted from HLA-matched sibling donor developed clonal proliferation of CD4+ Vβ3+ T cells caused by monoclonal EBV infection on day 99 after transplantation. Further analysis revealed that the CD4+ Vβ3+ T cells selectively harbored EBV genome, and these infected cells were derived from donor T cells.
  
  
  CONCLUSIONS
  Allogeneic HSCT with RIC is a safe and effective treatment for better overall survival and less regimen-related toxicity in patients with CAEBV. Our first pediatric case reported in the literature suggests that we should consider the possibility of persistent EBV infection in donor T cells as well as the relapse in recipient cells if EBV load increases after allogeneic HSCT.
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sasahara
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Chung Yeng
authors.initials: CY
authors.lastname: Looi
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Katayama
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Nobu
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Meri
authors.initials: M
authors.lastname: Ouchi
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horino
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Moriya
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nanjyo
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Masaei
authors.initials: M
authors.lastname: Onuma
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitazawa
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Irie
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Niizuma
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Uchiyama
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Rikiishi
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kumaki
authors.affiliation: Division of Blood Transfusion, Tohoku University Hospital, Sendai, Miyagi, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Minegishi
authors.affiliation: Department of Pediatrics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Wada
authors.affiliation: Department of Pediatrics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuchiya
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
mesh_terms: D000293:Adolescent; D015704:CD4 Antigens / Q000378:metabolism; D002648:Child; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000628:therapy* / Q000635:transmission / Q000821:virology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015704:CD4 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: T-cell receptor repertoire analysis; allogeneic hematopoietic stem cell transplantation; chronic active Epstein-Barr virus infection; microsatellite analysis; reduced-intensity conditioning