{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:49:42Z","timestamp":1791301782532,"version":"4.1.0"},"reference-count":26,"publisher":"American Society of Hematology","issue":"15","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CD19-directed chimerical antigen receptor T-cell (CAR-T) products have gained US Food and Drug Administration approval for systemic large B-cell lymphoma. Because of concerns about potential immune cell-associated neurotoxicity syndrome (ICANS), patients with primary central nervous system (CNS) lymphoma (PCNSL) were excluded from all pivotal CAR-T studies. We conducted a phase 1\/2 clinical trial of tisagenlecleucel in a highly refractory patients with PCNSL and significant unmet medical need. Here, we present results of 12 relapsed patients with PCNSL who were treated with tisagenlecleucel and followed for a median time of 12.2 months (range, 3.64-23.5). Grade 1 cytokine release syndrome was observed in 7\/12 patients (58.3%), low-grade ICANS in 5\/12 (41.6%) patients, and only 1 patient experienced grade 3 ICANS. Seven of 12 patients (58.3%) demonstrated response, including a complete response in 6\/12 patients (50%). There were no treatment-related deaths. Three patients had ongoing complete remission at data cutoff. Tisagenlecleucel expanded in the peripheral blood and trafficked to the CNS. Exploratory analysis identified T-cell, CAR T, and macrophage gene signatures in cerebrospinal fluid following infusion when compared with baseline. Overall, tisagenlecleucel was well tolerated and resulted in a sustained remission in 3\/7 (42.9%) of initial responders. These data suggest that tisagenlecleucel is safe and effective in this highly refractory patient population. This trial was registered at www.clinicaltrials.gov as #NCT02445248.<\/jats:p>","DOI":"10.1182\/blood.2021014738","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T15:04:28Z","timestamp":1644937468000},"page":"2306-2315","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":150,"title":["Safety and efficacy of tisagenlecleucel in primary CNS lymphoma: a phase 1\/2 clinical trial"],"prefix":"10.1182","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-5694","authenticated-orcid":false,"given":"Matthew J.","family":"Frigault","sequence":"first","affiliation":[{"name":"Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA;"},{"name":"Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, 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