{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:48:35Z","timestamp":1791301715732,"version":"4.1.0"},"reference-count":13,"publisher":"American Society of Hematology","issue":"11","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,9,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chimeric antigen receptor (CAR) T cells targeting CD19 have emerged as a leading engineered T-cell therapy for relapsed\/refractory B-cell non-Hodgkin lymphoma. The phase 1\/2 clinical trials that led to US Food and Drug Administration approval excluded patients with central nervous system (CNS) involvement, due to strict eligibility criteria. Here, we report on our institutional experience with 8 secondary CNS lymphoma patients treated with commercial tisagenlecleucel. No patient experienced greater than grade 1 neurotoxicity, and no patient required tocilizumab or steroids for CAR T-cell\u2013mediated toxicities. Biomarker analysis suggested CAR T-cell expansion, despite the absence of systemic disease, and early response assessments demonstrated activity of IV infused CAR T cells within the CNS space.<\/jats:p>","DOI":"10.1182\/blood.2019001694","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T21:24:04Z","timestamp":1563485044000},"page":"860-866","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":219,"title":["Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma"],"prefix":"10.1182","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-5694","authenticated-orcid":false,"given":"Matthew J.","family":"Frigault","sequence":"first","affiliation":[{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center,"},{"name":"Blood and Marrow Transplant Program, Massachusetts General Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorg","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center,"},{"name":"Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital Cancer Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5859-7562","authenticated-orcid":false,"given":"Maria","family":"Martinez-Lage","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3111-0221","authenticated-orcid":false,"given":"Mark","family":"Leick","sequence":"additional","affiliation":[{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan D.","family":"Choi","sequence":"additional","affiliation":[{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center,"},{"name":"Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-8974","authenticated-orcid":false,"given":"Zachariah","family":"DeFilipp","sequence":"additional","affiliation":[{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center,"},{"name":"Blood and Marrow Transplant Program, Massachusetts General Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Bin","family":"Chen","sequence":"additional","affiliation":[{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center,"},{"name":"Blood and Marrow Transplant Program, Massachusetts General Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-9257","authenticated-orcid":false,"given":"Jeremy","family":"Abramson","sequence":"additional","affiliation":[{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center,"},{"name":"Center for Lymphoma, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Crombie","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Armand","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Panzini","sequence":"additional","affiliation":[{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren S.","family":"Riley","sequence":"additional","affiliation":[{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7578-0393","authenticated-orcid":false,"given":"Marcela V.","family":"Maus","sequence":"additional","affiliation":[{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center,"},{"name":"Blood and Marrow Transplant Program, Massachusetts General Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"26","key":"2020021109181147700_B1","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N Engl J Med"},{"issue":"1","key":"2020021109181147700_B2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1056\/NEJMoa1804980","article-title":"Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma","volume":"380","author":"Schuster","year":"2019","journal-title":"N Engl J Med"},{"issue":"20","key":"2020021109181147700_B3","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1182\/blood-2018-12-893396","article-title":"Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells","volume":"133","author":"Karschnia","year":"2019","journal-title":"Blood"},{"issue":"2","key":"2020021109181147700_B4","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","article-title":"Current concepts in the diagnosis and management of cytokine release syndrome [published correction appears in Blood. 2016;128(11):1533]","volume":"124","author":"Lee","year":"2014","journal-title":"Blood"},{"key":"2020021109181147700_B5","unstructured":"US Department of Health and Human Services . Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. https:\/\/ctep.cancer.gov\/protocolDevelopment\/electronic_applications\/docs\/CTCAE_v5_Quick_Reference_8.5x11.pdf. Accessed 29 July 2019."},{"issue":"4","key":"2020021109181147700_B6","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol Blood Marrow Transplant"},{"issue":"8","key":"2020021109181147700_B7","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1056\/NEJMc1704610","article-title":"Anti-CD19 CAR T cells in CNS diffuse large-B-cell lymphoma","volume":"377","author":"Abramson","year":"2017","journal-title":"N Engl J Med"},{"issue":"21","key":"2020021109181147700_B8","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1182\/blood-2017-06-786129","article-title":"Cellular kinetics of CTL019 in relapsed\/refractory B-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia","volume":"130","author":"Mueller","year":"2017","journal-title":"Blood"},{"issue":"1","key":"2020021109181147700_B9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1158\/2159-8290.CD-NB2017-169","article-title":"JCAR015 in ALL: a root-cause investigation","volume":"8","year":"2018","journal-title":"Cancer Discov"},{"issue":"6","key":"2020021109181147700_B10","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41591-018-0041-7","article-title":"CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade","volume":"24","author":"Giavridis","year":"2018","journal-title":"Nat Med"},{"issue":"6","key":"2020021109181147700_B11","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41591-018-0036-4","article-title":"Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells","volume":"24","author":"Norelli","year":"2018","journal-title":"Nat Med"},{"issue":"6","key":"2020021109181147700_B12","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1158\/2159-8290.CD-16-0040","article-title":"Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia","volume":"6","author":"Teachey","year":"2016","journal-title":"Cancer Discov"},{"issue":"12","key":"2020021109181147700_B13","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1158\/2159-8290.CD-17-0698","article-title":"Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells","volume":"7","author":"Gust","year":"2017","journal-title":"Cancer Discov"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/134\/11\/860\/1554534\/bloodbld2019001694.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/134\/11\/860\/1554534\/bloodbld2019001694.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T01:30:23Z","timestamp":1663983023000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/134\/11\/860\/273869\/Tisagenlecleucel-CAR-Tcell-therapy-in-secondary"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,12]]},"references-count":13,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,9,12]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2019001694","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.736222499.793563215","asserted-by":"object"}]},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,12]]}}}