{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T15:18:48Z","timestamp":1761664728782,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Background: Adult T-cell leukemia\/lymphoma (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) after a long latent infection. HTLV-1 induces the indolent or aggressive type of leukemia in 5% of HTLV-1 carriers. ATL, especially the aggressive type, is resistant to multi-agent chemotherapy. The indolent type often progresses to the aggressive type. Even in the most indolent-type cases, that is, smoldering ATL, the average survival time is 55.0 months. Case Presentation: Five patients with ATL were followed up for their clinical course after amplified natural killer cell (ANK) therapy. Four patients who received ANK therapy as first-line therapy achieved complete remission and showed long-term survival without aggressive conversion or relapse for more than 5 years. One patient was treated with multiagent chemotherapy due to acute exacerbation but relapsed 2 months later. She was subsequently treated with radiation and ANK therapy and survived for more than 6 years. Furthermore, ANK therapy enhanced the immune function of ATL patients to a level higher than that of normal individuals. Conclusions: ANK therapy has great potential as first-line treatment for ATL.<\/jats:p>","DOI":"10.3390\/reports7030080","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T11:51:46Z","timestamp":1726746706000},"page":"80","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Long-Term Survival of Patients with Adult T-Cell Leukemia\/Lymphoma Treated with Amplified Natural Killer Cell Therapy"],"prefix":"10.3390","volume":"7","author":[{"given":"Yuji","family":"Okubo","sequence":"first","affiliation":[{"name":"Higashinotohin Clinic, 338 Empukuji, Nakagyo, Kyoto 604-8175, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sho","family":"Nagai","sequence":"additional","affiliation":[{"name":"Ebino Centro Clinic, 1007-4, Uwae, Ebino, Miyazaki 889-4304, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuta","family":"Katayama","sequence":"additional","affiliation":[{"name":"Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, 1-9-6, Senda, Naka, Hiroshima 730-8619, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiro","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Kitamura Clinic, 4-3-8, Nishiki, Onojo, Fukuoka 816-0935, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhisa","family":"Hiwaki","sequence":"additional","affiliation":[{"name":"Hiwaki Clinic, 2-14-65, Asano, Kokurakita, Kitakyushu, Fukuoka 802-0001, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6716-5745","authenticated-orcid":false,"given":"Keisuke","family":"Teshigawara","sequence":"additional","affiliation":[{"name":"Higashinotohin Clinic, 338 Empukuji, Nakagyo, Kyoto 604-8175, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1182\/blood.V50.3.481.481","article-title":"Adult T-Cell Leukemia: Clinical and Hematologic Features of 16 Cases","volume":"50","author":"Uchiyama","year":"1977","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and Isolation of Type C Retrovirus Particles from Fresh and Cultured Lymphocytes of a Patient with Cutaneous T-Cell Lymphoma","volume":"77","author":"Poiesz","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S0140-6736(87)92358-0","article-title":"Breaking the Cycle of HTLV-I Transmission via Carrier Mothers\u2019 Milk","volume":"2","author":"Hino","year":"1987","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6047","DOI":"10.1038\/sj.onc.1208979","article-title":"Natural History of Adult T-Cell Leukemia\/Lymphoma and Approaches to Therapy","volume":"24","author":"Taylor","year":"2005","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lymphoma Study Group (1984\u20131987) (1991). Major Prognostic Factors of Patients with Adult T-Cell Leukemia-Lymphoma: A Cooperative Study. Leuk. Res., 15, 81\u201390.","DOI":"10.1016\/0145-2126(91)90087-A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s00432-004-0600-9","article-title":"Serum-Soluble Interleukin-2 Receptor (sIL-2R) Level Determines Clinical Outcome in Patients with Aggressive Non-Hodgkin\u2019s Lymphoma: In Combination with the International Prognostic Index","volume":"131","author":"Goto","year":"2005","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/j.1365-2141.1991.tb08051.x","article-title":"Diagnostic Criteria and Classification of Clinical Subtypes of Adult T-Cell Leukaemia-Lymphoma: A Report from the Lymphoma Study Group (1984\u201387)","volume":"79","author":"Shimoyama","year":"1991","journal-title":"Br. J. Haematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1200\/JCO.2011.38.2101","article-title":"Prognostic Index for Acute- and Lymphoma-Type Adult T-Cell Leukemia\/Lymphoma","volume":"30","author":"Katsuya","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1182\/blood-2017-01-757542","article-title":"Prognostic Index for Chronic- and Smoldering-Type Adult T-Cell Leukemia-Lymphoma","volume":"130","author":"Katsuya","year":"2017","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1182\/blood.V71.4.1021.1021","article-title":"Soluble Interleukin 2 Receptors in Sera of Japanese Patients with Adult T Cell Leukemia Mark Activity of Disease","volume":"71","author":"Yasuda","year":"1988","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3961","DOI":"10.1182\/blood-2010-11-316794","article-title":"Type of Skin Eruption Is an Independent Prognostic Indicator for Adult T-Cell Leukemia\/Lymphoma","volume":"117","author":"Sawada","year":"2011","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"El Hajj, H., Tsukasaki, K., Cheminant, M., Bazarbachi, A., Watanabe, T., and Hermine, O. (2020). Novel Treatments of Adult T Cell Leukemia Lymphoma. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01062"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Teshigawara, K., Nagai, S., Bai, G., Okubo, Y., Chagan-Yasutan, H., and Hattori, T. (2018). Successful Amplified-Natural-Killer Cell (ANK) Therapy Administered to a Patient with Smoldering Adult T-Cell Leukemia in Acute Crisis. Reports, 1.","DOI":"10.3390\/reports1020013"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0022-1759(86)90511-9","article-title":"Europium-labelled target cells in an assay of natural killer cell activity II. A novel non-radioactive method based on time-resolved fluorescence. Significance and specificity of the method","volume":"21","author":"Blomberg","year":"1986","journal-title":"J. Immunol. Methods"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1200\/JCO.18.00501","article-title":"Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report","volume":"10","author":"Cook","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_16","unstructured":"(2024, August 26). Japanese Society of Hematology Guideline for Treatment of Haematopoietic Tumors. Available online: http:\/\/www.jshem.or.jp\/gui-hemali\/index.html."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1038\/s41409-019-0446-z","article-title":"VCAP-AMP-VECP as a preferable induction chemotherapy in transplant-eligible patients with aggressive adult T-cell leukemia-lymphoma: A propensity score analysis","volume":"54","author":"Fuji","year":"2019","journal-title":"Bone Marrow Transplant."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1053\/j.seminhematol.2020.11.003","article-title":"Memory-like Natural Killer Cells for Cancer Immunotherapy","volume":"57","author":"Gang","year":"2020","journal-title":"Semin. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"205796","DOI":"10.1155\/2014\/205796","article-title":"Utilizing cytokines to function-enable human NK cells for the immunotherapy of cancer","volume":"2014","author":"Romee","year":"2014","journal-title":"Scientifica"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1182\/blood-2007-09-077438","article-title":"Human Natural Killer Cells","volume":"112","author":"Caligiuri","year":"2008","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5047","DOI":"10.1182\/blood-2007-10-118539","article-title":"High Frequency of CD4+FoxP3+ Cells in HTLV-1 Infection: Inverse Correlation with HTLV-1\u2013Specific CTL Response","volume":"111","author":"Toulza","year":"2008","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1182\/blood-2017-01-761874","article-title":"Prognostic Relevance of Integrated Genetic Profiling in Adult T-Cell Leukemia\/Lymphoma","volume":"131","author":"Kataoka","year":"2018","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Futsch, N., Prates, G., Mahieux, R., Casseb, J., and Dutartre, H. (2018). Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases. Viruses, 10.","DOI":"10.3390\/v10120691"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Higuchi, Y., Yasunaga, J., and Matsuoka, M. (2022). HTLV-1\u2019s Foxy Strategy for Survival and Transmission. Front. Virol., 1.","DOI":"10.3389\/fviro.2021.792659"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1099\/vir.0.79921-0","article-title":"Tax Protein of Human T-Cell Leukaemia Virus Type 1 Induces Interleukin 17 Gene Expression in T Cells","volume":"85","author":"Dodon","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13740","DOI":"10.1073\/pnas.1922884117","article-title":"HTLV-1 Induces T Cell Malignancy and Inflammation by Viral Antisense Factor-Mediated Modulation of the Cytokine Signaling","volume":"117","author":"Higuchi","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and Cancer","volume":"420","author":"Coussens","year":"2002","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/jcb.240460405","article-title":"Cytokine Induction in HTLV-I Associated Myelopathy and Adult T-Cell Leukemia: Alternate Molecular Mechanisms Underlying Retroviral Pathogenesis","volume":"46","author":"Tendler","year":"1991","journal-title":"J. Cell Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1395123","DOI":"10.1080\/2162402X.2017.1395123","article-title":"Activated Human Primary NK Cells Efficiently Kill Colorectal Cancer Cells in 3D Spheroid Cultures Irrespectively of the Level of PD-L1 Expression","volume":"7","author":"Lanuza","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1084\/jem.20021747","article-title":"Stress Signals Activate Natural Killer Cells","volume":"196","author":"Long","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e244619","DOI":"10.1136\/bcr-2021-244619","article-title":"Successful Treatment of Smouldering Human T Cell Leukemia i Type1 Associated Bronchiolitis and Alveolar Abnormalities with Amplified Natural Killer Therapy","volume":"14","author":"Nagai","year":"2021","journal-title":"BMJ Case Rep."}],"container-title":["Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2571-841X\/7\/3\/80\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:59:50Z","timestamp":1760111990000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2571-841X\/7\/3\/80"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,19]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["reports7030080"],"URL":"https:\/\/doi.org\/10.3390\/reports7030080","relation":{},"ISSN":["2571-841X"],"issn-type":[{"type":"electronic","value":"2571-841X"}],"subject":[],"published":{"date-parts":[[2024,9,19]]}}}