A case series of CAEBV of children and young adults treated with reduced-intensity conditioning and allogeneic bone marrow transplantation: a single-center study.
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.


PATIENTS AND 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.
['Watanabe|Yuko|Y|', 'Sasahara|Yoji|Y|', 'Satoh|Miki|M|', 'Looi|Chung Yeng|CY|', 'Katayama|Saori|S|', 'Suzuki|Tasuku|T|', 'Suzuki|Nobu|N|', 'Ouchi|Meri|M|', 'Horino|Satoshi|S|', 'Moriya|Kunihiko|K|', 'Nanjyo|Yuka|Y|', 'Onuma|Masaei|M|', 'Kitazawa|Hiroshi|H|', 'Irie|Masahiro|M|', 'Niizuma|Hidetaka|H|', 'Uchiyama|Toru|T|', 'Rikiishi|Takeshi|T|', 'Kumaki|Satoru|S|', 'Minegishi|Masayoshi|M|', 'Wada|Taizo|T|', 'Yachie|Akihiro|A|', 'Tsuchiya|Shigeru|S|', 'Kure|Shigeo|S|']
D000293:Adolescent D015704:CD4 Antigens D002648:Child D020031:Epstein-Barr Virus Infections D005260:Female D018380:Hematopoietic Stem Cell Transplantation D004854:Herpesvirus 4, Human D006801:Humans D008213:Lymphocyte Activation D016131:Lymphocyte Subsets D008297:Male D016693:Receptors, Antigen, T-Cell, alpha-beta D014019:Tissue Donors D019172:Transplantation Conditioning D014184:Transplantation, Homologous D016896:Treatment Outcome D055815:Young Adult
reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation microsatellite analysis T-cell receptor repertoire analysis chronic active Epstein-Barr virus infection