{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:37:55Z","timestamp":1776940675806,"version":"3.51.4"},"reference-count":10,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Haematol"],"published-print":{"date-parts":[[2023]]},"abstract":"<jats:p>CD19-directed chimeric antigen receptor (CAR) T-cell therapy has been widely used and is highly effective for B-cell lymphoid malignancies. Immune-mediated adverse effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occur in the acute phase and are monophasic after CAR T-cell therapy. However, late-onset inflammatory and neurological toxicities have not been well studied. We encountered a patient with recurrent late-onset inflammatory toxicities and progressive dysautonomia after CD19-directed CAR T-cell therapy. A 69-year-old man was treated with CD19-directed CAR T-cell therapy for transformed follicular lymphoma. Triphasic inflammation with stomatitis, cytopenia, and noninfectious pneumonia was first observed 7 months after CAR T-cell infusion. Progressive dysautonomia was also observed and eventually fatal. Residual CAR T cells, predominantly central memory CD4+ cells, were detectable in peripheral blood approximately 1 year after CAR T-cell infusion. The cytokine profile with the lack of tumor necrosis factor-\u03b1, interferon-\u03b3, and interleukin-1\u03b2 elevation in the peripheral blood and cerebrospinal fluid was inconsistent with that of typical CRS or ICANS. The persistence of central memory CD4+ CAR T cells might be associated with unique manifestations of late-onset immune-mediated adverse effects. More cases should be accumulated to elucidate the mechanism and establish the optimal management strategy of late-onset immune-mediated toxicities previously unrecognized. <\/jats:p>","DOI":"10.1159\/000530743","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T21:00:36Z","timestamp":1682110836000},"page":"338-342","source":"Crossref","is-referenced-by-count":5,"title":["Recapitulated Late-Onset Inflammatory Toxicities and Progressive Dysautonomia with Persistence of Central Memory CD4+ Chimeric Antigen Receptor T Cells in a Case of Transformed Follicular Lymphoma: Case Report"],"prefix":"10.1159","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0388-3836","authenticated-orcid":false,"given":"Mitsutaka","family":"Nishimoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruhito","family":"Takakuwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatomo","family":"Kuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Makuuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-8459","authenticated-orcid":false,"given":"Hiroshi","family":"Okamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3025-723X","authenticated-orcid":false,"given":"Yasuhiro","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Koh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroto","family":"Namba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Hino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirohisa","family":"Nakamae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.10.478"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.12.758"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.577027"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-348540"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130059"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/nri3839"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004889"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-022-00629-1"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01564-7"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04390-6"}],"container-title":["Acta Haematologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/aha\/article-pdf\/146\/4\/338\/3984836\/000530743.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/aha\/article-pdf\/146\/4\/338\/3984836\/000530743.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:27:27Z","timestamp":1745422047000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000530743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023]]},"references-count":10,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,8,10]]},"published-print":{"date-parts":[[2023,8,15]]}},"URL":"https:\/\/doi.org\/10.1159\/000530743","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.22672621","asserted-by":"subject"}]},"ISSN":["0001-5792","1421-9662"],"issn-type":[{"value":"0001-5792","type":"print"},{"value":"1421-9662","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023]]}}}