title: Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs.
abstract: Extranodal NK/T-cell lymphoma (ENKTCL) is associated with latent Epstein-Barr virus (EBV) infection and frequent relapse even after complete response (CR) to intensive chemotherapy and radiotherapy. The expression of EBV proteins in the tumor provides targets for adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL). To evaluate the efficacy and safety of EBV latent membrane protein (LMP)-1 and LMP-2a-specific CTLs (LMP1/2a CTLs) stimulated with LMP1/2a RNA-transferred dendritic cells, we treated 10 ENKTCL patients who showed complete response to induction therapy. Patients who completed and responded to chemotherapy, radiotherapy, and/or high-dose therapy followed by stem cell transplantation (HDT/SCT) were eligible to receive eight doses of 2 × 10(7) LMP1/2a CTLs/m(2). Following infusion, there were no immediate or delayed toxicities. The 4-year overall survival (OS) and progression-free survival (PFS) were 100%, and 90% (95% CI: 71.4 to 100%) respectively with a median follow-up of 55·5 months. Circulating IFN-γ secreting LMP1 and LMP2a-specific T cells within the peripheral blood corresponded with decline in plasma EBV DNA levels in patients. Adoptive transfer of LMP1/2a CTLs in ENKTCL patients is a safe and effective postremission therapeutic approach. Further randomized studies will be needed to define the role of EBV-CTLs in preventing relapse of ENKTCL.
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; Institute for Translational Research and Molecular Imaging, College of Medicine, The Catholic University of Korea, Seoul, Korea; Catholic Lymphoma Study Group (CULG), Catholic Institute of Cell Therapy, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seok-Goo
authors.initials: SG
authors.lastname: Cho
authors.affiliation: Institute for Translational Research and Molecular Imaging, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Nayoun
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Sohn
authors.affiliation: Department of Medical Lifescience, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Suk Kyeong
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Medical Lifescience, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sang Taek
authors.initials: ST
authors.lastname: Oh
authors.affiliation: Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, Korea; Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyun-Il
authors.initials: HI
authors.lastname: Cho
authors.affiliation: Department of Preventive Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyeon Woo
authors.initials: HW
authors.lastname: Yim
authors.affiliation: Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung Eun
authors.initials: SE
authors.lastname: Jung
authors.affiliation: Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Gyeongsin
authors.initials: G
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Byung-Ock
authors.initials: BO
authors.lastname: Choi
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Soo Whan
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Nak Gyun
authors.initials: NG
authors.lastname: Chung
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jong Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Medical Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Young Seon
authors.initials: YS
authors.lastname: Hong
authors.affiliation: Department of Microbiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, Korea. Electronic address: kimtg@catholic.ac.kr.
authors.forename: Tai-Gyu
authors.initials: TG
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D003713:Dendritic Cells / Q000166:cytology / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015316:Genetic Therapy; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D054391:Lymphoma, Extranodal NK-T-Cell / Q000276:immunology / Q000628:therapy*; D008297:Male; D009364:Neoplasm Recurrence, Local; D012008:Recurrence; D012074:Remission Induction; D033581:Stem Cell Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*; D016896:Treatment Outcome; D014763:Viral Matrix Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins