{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:20:55Z","timestamp":1792120855163,"version":"4.4.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["24K11563"],"award-info":[{"award-number":["24K11563"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chimeric antigen receptor (CAR) T cell therapy has significantly improved outcomes for patients with refractory B cell lymphoma. However, rare cases of secondary T cell lymphomas have raised safety concerns. Here, we present a case of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) that developed eight months following CD19-directed CAR T cell therapy (lisocabtagene maraleucel) in a 66-year-old male patient with recurrent diffuse large B cell lymphoma. The patient initially achieved complete remission but later developed a subcutaneous mass and systemic lymphadenopathy. Histopathology and flow cytometry confirmed a diagnosis of PTCL-NOS with a CD3\u2009+\u2009, CD8\u2009+\u2009, and CD30\u2009+\u2009phenotype, as well as clonal T cell receptor gene rearrangements. No immunoglobulin rearrangements were detected, ruling out a lineage switch. Furthermore, the CAR transgene was undetectable by RNA-in situ hybridization, and flow cytometry showed no CAR protein expression, suggesting that the lymphoma was not caused by CAR gene integration. This case highlights the importance of re-biopsy in cases of suspected relapse following CAR T cell therapy, and emphasizes the need for long-term monitoring. While a direct causal link remains unclear, industry\u2013academia collaboration is crucial for investigating the mechanisms underlying secondary T cell malignancies and improving the safety of CAR T cell therapy.<\/jats:p>","DOI":"10.1007\/s12185-025-04074-1","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:51:17Z","timestamp":1761054677000},"page":"815-819","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Peripheral T cell lymphoma following CD19-targeted chimeric antigen receptor T cell therapy"],"prefix":"10.1007","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8131-3401","authenticated-orcid":false,"given":"Hiro","family":"Tatetsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taichi","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikiko","family":"Ueno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Miyasato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asami","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Shichijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Higuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiro","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kisato","family":"Nosaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Mikami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennosuke","family":"Karube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichirou","family":"Yasunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"4074_CR1","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41571-023-00754-1","volume":"20","author":"KM Cappell","year":"2023","unstructured":"Cappell KM, Kochenderfer JN. Long-term outcomes following CAR T cell therapy: what we know so far. Nat Rev Clin Oncol. 2023;20:359\u201371.","journal-title":"Nat Rev Clin Oncol"},{"key":"4074_CR2","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1182\/blood.2024024166","volume":"143","author":"M Elsallab","year":"2024","unstructured":"Elsallab M, Ellithi M, Lunning MA, D\u2019Angelo C, Ma J, Perales MA, et al. Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA adverse events reporting system. Blood. 2024;143:2099\u2013105.","journal-title":"Blood"},{"key":"4074_CR3","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1056\/NEJMp2400209","volume":"390","author":"N Verdun","year":"2024","unstructured":"Verdun N, Marks P. Secondary cancers after chimeric antigen receptor t-cell therapy. N Engl J Med. 2024;390:584\u20136.","journal-title":"N Engl J Med"},{"key":"4074_CR4","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/s41591-023-02767-w","volume":"30","author":"BL Levine","year":"2024","unstructured":"Levine BL, Pasquini MC, Connolly JE, Porter DL, Gustafson MP, Boelens JJ, et al. Unanswered questions following reports of secondary malignancies after CAR-T cell therapy. Nat Med. 2024;30:338\u201341.","journal-title":"Nat Med"},{"key":"4074_CR5","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1126\/science.1088547","volume":"302","author":"S Hacein-Bey-Abina","year":"2003","unstructured":"Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science. 2003;302:415\u20139.","journal-title":"Science"},{"key":"4074_CR6","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/s41591-024-02826-w","volume":"30","author":"G Ghilardi","year":"2024","unstructured":"Ghilardi G, Fraietta JA, Gerson JN, Van Deerlin VM, Morrissette JJD, Caponetti GC, et al. T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy. Nat Med. 2024;30:984\u20139.","journal-title":"Nat Med"},{"key":"4074_CR7","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1182\/blood.2021010813","volume":"138","author":"DC Bishop","year":"2021","unstructured":"Bishop DC, Clancy LE, Simms R, Burgess J, Mathew G, Moezzi L, et al. Development of CAR T-cell lymphoma in 2 of 10 patients effectively treated with piggyBac-modified CD19 CAR T cells. Blood. 2021;138:1504\u20139.","journal-title":"Blood"},{"key":"4074_CR8","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1182\/blood.2021010858","volume":"138","author":"KP Micklethwaite","year":"2021","unstructured":"Micklethwaite KP, Gowrishankar K, Gloss BS, Li Z, Street JA, Moezzi L, et al. Investigation of product-derived lymphoma following infusion of piggyBac-modified CD19 chimeric antigen receptor T cells. Blood. 2021;138:1391\u2013405.","journal-title":"Blood"},{"key":"4074_CR9","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/bjh.17499","volume":"194","author":"SJ Harrison","year":"2021","unstructured":"Harrison SJ, Perrot A, Alegre A, Simpson D, Wang MC, Spencer A, et al. Subgroup analysis of ICARIA-MM study in relapsed\/refractory multiple myeloma patients with high-risk cytogenetics. 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Clin Cancer Res. 2024;30:4690\u2013700.","journal-title":"Clin Cancer Res"},{"key":"4074_CR14","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1056\/NEJMoa2401361","volume":"390","author":"MP Hamilton","year":"2024","unstructured":"Hamilton MP, Sugio T, Noordenbos T, Shi S, Bulterys PL, Liu CL, et al. Risk of second tumors and T-cell lymphoma after CAR T-cell therapy. N Engl J Med. 2024;390:2047\u201360.","journal-title":"N Engl J Med"},{"key":"4074_CR15","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1182\/blood.2024025828","volume":"144","author":"J Hu","year":"2024","unstructured":"Hu J, Dunbar CE. T-cell lymphomas in recipients of CAR-T cells: assessing risks and causalities. Blood. 2024;144:2473\u201381.","journal-title":"Blood"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-025-04074-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-025-04074-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-025-04074-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T07:05:20Z","timestamp":1769238320000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-025-04074-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":15,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["4074"],"URL":"https:\/\/doi.org\/10.1007\/s12185-025-04074-1","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,21]]},"assertion":[{"value":"28 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"HT has received honoraria from AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai, Ono, Nihon Shinyaku, Novartis, SymBio Pharmaceuticals Limited, Takeda Pharmaceutical, Meiji Seika Pharma, Gilead Sciences, and Abbvie Inc., and patents and royalties from Mesoblasts. Koji Kato received honoraria from Novartis, Chugai, Meiji, Gilead Sciences, Kyowa Kirin, and Bristol Myers Squibb and research funding from Chugai, Takeda, AbbVie, Novartis, Eisai, Janssen, Ono, Meiji, Daiichi Sankyo, MSD, Bristol Myers Squibb, Gilead Sciences, and Astellas. SU has received honoraria from Sobi\u00a0Japan,\u00a0Asahi Kasei Pharma Corporation, Alexion, Novartis Pharmaceuticals, Chugai Pharmaceutical Co.,\u00a0and Argenx\u00a0Japan K.K. KN is an editor for the\n                      International Journal of Hematology\n                      and has received honoraria from Bristol Myers Squibb, Chugai Pharmaceutical, Eisai, Meiji Seika Pharma, Abbvie Inc., Minophagen, Dai-ichi Sankyo, and Kyowa Kirin and research funding from Kyowa Kirin and Chugai Pharmaceutical. JY has received research funding from Eisai. The rest of the authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was approved by the Institutional Review Board of Kumamoto University Hospital (No. 499) and conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from the patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}