{"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":1791301715329,"version":"4.1.0"},"reference-count":20,"publisher":"American Society of Hematology","issue":"20","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD19-directed chimeric antigen receptor (CD19CAR) T-cell therapy has been successful in treating several B-cell lineage malignancies, including B-cell non-Hodgkin lymphoma (NHL). This modality has not yet been extended to NHL manifesting in the central nervous system (CNS), primarily as a result of concerns for potential toxicity. CD19CAR T cells administered IV are detectable in cerebrospinal fluid (CSF), suggesting that chimeric antigen receptor (CAR) T cells can migrate from the periphery into the CNS, where they can potentially mediate antilymphoma activity. Here, we report the outcome of a subset of patients with primary CNS lymphoma (PCNSL; n = 5) who were treated with CD19CAR T cells in our ongoing phase 1 clinical trial. All patients developed grade \u2265 1 cytokine release syndrome and neurotoxicity post-CAR T-cell infusion; toxicities were reversible and tolerable, and there were no treatment-related deaths. At initial disease response, 3 of 5 patients (60%; 90% confidence interval, 19-92%) seemed to achieve complete remission, as indicated by resolution of enhancing brain lesions; the remaining 2 patients had stable disease. Although the study cohort was small, we demonstrate that using CD19CAR T cells to treat PCNSL can be safe and feasible. This trial was registered at www.clinicaltrials.gov as #NCT02153580.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020004106","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T21:57:56Z","timestamp":1631051876000},"page":"4059-4063","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":115,"title":["CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma"],"prefix":"10.1182","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5292-8298","authenticated-orcid":false,"given":"Tanya","family":"Siddiqi","sequence":"first","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Suzette","family":"Blanchard","sequence":"additional","affiliation":[{"name":"Department of Computational and Quantitative Medicine\/Beckman Research Institute, City of Hope Medical Center, Duarte, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie R.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Hematology T-Cell Therapeutics Research Laboratories, City of Hope Medical Center, Duarte, CA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie L.","family":"Popplewell","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1464-5494","authenticated-orcid":false,"given":"L. Elizabeth","family":"Budde","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey L.","family":"Stiller","sequence":"additional","affiliation":[{"name":"Department of Computational and Quantitative Medicine\/Beckman Research Institute, City of Hope Medical Center, Duarte, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary C.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Project Development, City of Hope Medical Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vibhuti","family":"Vyas","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Forman","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"issue":"26","key":"2021102214042319500_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":"2021102214042319500_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":"10254","key":"2021102214042319500_B3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S0140-6736(20)31366-0","article-title":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study","volume":"396","author":"Abramson","year":"2020","journal-title":"Lancet."},{"issue":"20","key":"2021102214042319500_B4","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":"12","key":"2021102214042319500_B5","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."},{"issue":"8","key":"2021102214042319500_B6","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":"11","key":"2021102214042319500_B7","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1182\/blood.2019001694","article-title":"Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma","volume":"134","author":"Frigault","year":"2019","journal-title":"Blood."},{"issue":"1","key":"2021102214042319500_B8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-019-0838-y","article-title":"Axicabtagene ciloleucel CD19 CAR-T cell therapy results in high rates of systemic and neurologic remissions in ten patients with refractory large B cell lymphoma including two with HIV and viral hepatitis","volume":"13","author":"Abbasi","year":"2020","journal-title":"J Hematol Oncol."},{"issue":"4","key":"2021102214042319500_B9","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1080\/10428194.2019.1695052","article-title":"What a headache! Double-hit lymphoma with CNS recurrence - role of chimeric antigen receptor (CAR) T-cell therapy","volume":"61","author":"Rafelson","year":"2020","journal-title":"Leuk Lymphoma."},{"key":"2021102214042319500_B10","doi-asserted-by":"crossref","first-page":"7515","DOI":"10.1200\/JCO.2019.37.15_suppl.7515","article-title":"Lisocabtagene maraleucel (liso-cel) treatment of patients (pts) with relapsed\/refractory (R\/R) B-cell non-Hodgkin lymphoma (NHL) and secondary CNS lymphoma: Initial results from TRANSCEND NHL 001","volume":"37","author":"Abramson","year":"2019","journal-title":"J Clin Oncol."},{"issue":"1350","key":"2021102214042319500_B11","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.3389\/fonc.2019.01350","article-title":"CD19 and CD70 dual-target chimeric antigen receptor T-cell therapy for the treatment of relapsed and refractory primary central nervous system diffuse large B-cell lymphoma","volume":"9","author":"Tu","year":"2019","journal-title":"Front 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