{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:35:13Z","timestamp":1787841313925,"version":"build-2784847793"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\/background:<\/jats:title>\n                    <jats:p>Despite the success of chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive non-Hodgkin lymphoma (aNHL), some patients still fail treatment, and their prognosis is dismal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We performed a retrospective study of aNHL patients treated with axicabtagene ciloleucel (axi-cel) at two Mayo Clinic centers between 2018 and 2020. We evaluated predictive factors, toxicities, and responses to salvage regimens after CAR T-cell therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Thirty-four patients received axi-cel with a median length of hospitalization of 14 days. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome of any grade occurred in 91% and 41% of patients, respectively. Furthermore, 71% of patients responded to therapy, with 53% achieving a complete response (CR). The CRS grade and absolute lymphocyte count at leukapheresis (ALC\n                      <jats:sub>Leuk<\/jats:sub>\n                      ) correlated with CR and overall survival (OS), respectively. After a median follow-up of 6.8 months (interquartile range [IQR] 4.6\u201314.9), 15 patients (44%) showed progressive disease (PD). Most patients (60%) progressed during the first 3 months and had persistent CD19 tumor expression. Elevated C-reactive protein at baseline increased the risk of PD, whereas elevated ferritin increased PD and mortality risk. Twelve patients received salvage therapy, but only three responded. Median OS of relapsed\/refractory patients to axi-cel was 3 months (IQR 1.3\u20135.1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      The grade of CRS and ALC\n                      <jats:sub>Leuk<\/jats:sub>\n                      correlated with better outcomes to axi-cel therapy. In addition, elevated inflammatory markers at baseline were associated with PD and shorter survival. Relapses after treatment frequently occur within months after axi-cel infusion; they confer a poor prognosis and create an urgent need for novel and effective treatment options in this patient population.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.hemonc.2021.09.001","type":"journal-article","created":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T03:06:56Z","timestamp":1632107216000},"page":"133-143","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":7,"title":["Predictors and Management of Relapse to Axicabtagene Ciloleucel in Patients with Aggressive B-cell Lymphoma \u2606"],"prefix":"10.4103","volume":"16","author":[{"given":"Jose Vicente","family":"Forero-Forero","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division Hematology-Oncology, Mayo Clinic, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula A.","family":"Lengerke-Diaz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division Hematology-Oncology, Mayo Clinic, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eider","family":"Moreno-Cortes","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division Hematology-Oncology, Mayo Clinic, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Melody","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaid Abdel","family":"Rahman","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison C.","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division Hematology-Oncology, Mayo Clinic, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Kharfan-Dabaja","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Januario E.","family":"Castro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division Hematology-Oncology, Mayo Clinic, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"R1-20241211","first-page":"159","article-title":"Chimeric antigen receptor T cell therapy in oncology \u2013 pipeline at a glance: analysis of the Clinical- Trials.gov database","author":"Moreno-Cortes","year":"2021","journal-title":"Crit Rev Oncol Hematol"},{"key":"R2-20241211","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1158\/1078-0432.CCR-18-2743","article-title":"FDA approval summary: axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma","volume":"25","author":"Bouchkouj","year":"2019","journal-title":"Clin Cancer Res"},{"key":"R3-20241211","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1158\/1078-0432.CCR-18-2035","article-title":"FDA approval summary: tisagenlecleucel for treatment of patients with relapsed or refractory B-cell Precursor acute lymphoblastic leukemia","volume":"25","author":"O\u2019Leary","year":"2019","journal-title":"Clin Cancer Res"},{"key":"R5-20241211","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"},{"key":"R6-20241211","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s40425-018-0460-5","article-title":"Chimeric antigen receptor (CAR) T therapies for the treatment of hematologic malignancies: clinical perspective and significance","volume":"6","author":"Boyiadzis","year":"2018","journal-title":"J ImmunoTher Cancer"},{"key":"R7-20241211","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"},{"key":"R8-20241211","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1200\/JCO.19.02103","article-title":"Axicabtagene ciloleucel in the non-trial setting: outcomes and correlates of response, resistance, and toxicity","volume":"38","author":"Jacobson","year":"2020","journal-title":"J Clin Oncol"},{"key":"R9-20241211","doi-asserted-by":"crossref","first-page":"4669","DOI":"10.1182\/bloodadvances.2020002118","article-title":"Outcomes in patients with DLBCL treated with commercial CAR T cells compared with alternate therapies","volume":"4","author":"Sermer","year":"2020","journal-title":"Blood Adv"},{"key":"R10-20241211","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1182\/blood-2017-03-769620","article-title":"Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study","volume":"130","author":"Crump","year":"2017","journal-title":"Blood"},{"key":"R11-20241211","doi-asserted-by":"crossref","first-page":"e344","DOI":"10.1016\/j.bbmt.2019.06.036","article-title":"Understanding and managing large B cell lymphoma relapses after chimeric antigen receptor T cell therapy","volume":"25","author":"Byrne","year":"2019","journal-title":"Biol Blood Marrow Transplant"},{"key":"R12-20241211","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrclinonc.2017.148","article-title":"Chimeric antigen receptor T-cell therapy \u2013 assessment and management of toxicities","volume":"15","author":"Neelapu","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"key":"R13-20241211","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"},{"key":"R14-20241211","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","volume":"124","author":"Lee","year":"2014","journal-title":"Blood"},{"key":"R15-20241211","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1016\/j.ymthe.2017.07.004","article-title":"Long-duration complete remissions of diffuse large B cell lymphoma after anti-CD19 chimeric antigen receptor T cell therapy","volume":"25","author":"Kochenderfer","year":"2017","journal-title":"Mol Ther"},{"key":"R16-20241211","doi-asserted-by":"crossref","first-page":"E209","DOI":"10.1002\/ajh.25505","article-title":"Outcomes of patients with large B-cell lymphomas and progressive disease following CD19-specific CAR T-cell therapy","volume":"94","author":"Chow","year":"2019","journal-title":"Am J Hematol"},{"key":"R17-20241211","doi-asserted-by":"crossref","DOI":"10.1182\/blood.2020006245","article-title":"Outcomes of patients with large B-cell lymphoma progressing after axicabtagene ciloleucel","author":"Spiegel","year":"2020","journal-title":"Blood"},{"key":"R18-20241211","doi-asserted-by":"crossref","first-page":"4898","DOI":"10.1182\/bloodadvances.2020002394","article-title":"Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma","volume":"4","author":"Locke","year":"2020","journal-title":"Blood Adv"},{"key":"R19-20241211","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":"2018","journal-title":"N Engl J Med"},{"key":"R20-20241211","doi-asserted-by":"crossref","first-page":"4106","DOI":"10.1182\/blood-2019-127094","article-title":"Peak lymphocyte count after CAR T Infusion is a clinically accessible test that correlates with clinical response in axicabtagene ciloleucel therapy for lymphoma","volume":"134","author":"Novo","year":"2019","journal-title":"Blood"},{"key":"R21-20241211","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.3390\/cells9051225","article-title":"Current Challenges in providing good leukapheresis products for manufacturing of CAR-T cells for patients with relapsed\/refractory NHL or ALL","volume":"9","author":"Korell","year":"2020","journal-title":"Cells"},{"key":"R22-20241211","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1002\/ajh.25951","article-title":"Commercial anti-CD19 CAR T cell therapy for patients with relapsed\/refractory aggressive B cell lymphoma in a European center","volume":"95","author":"Sesques","year":"2020","journal-title":"Am J Hematol"},{"key":"R23-20241211","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.immuni.2019.06.021","article-title":"Pas de Deux: Control of anti-tumor immunity by cancer-associated inflammation","volume":"51","author":"Shalapour","year":"2019","journal-title":"Immunity"}],"container-title":["Hematology\/Oncology and Stem Cell Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1658387621000844?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1658387621000844?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ovid.com\/10.1016\/j.hemonc.2021.09.001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:49:26Z","timestamp":1787838566000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1016\/j.hemonc.2021.09.001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,17]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.1016\/j.hemonc.2021.09.001","relation":{},"ISSN":["1658-3876","2589-0646"],"issn-type":[{"value":"1658-3876","type":"print"},{"value":"2589-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,17]]},"assertion":[{"value":"2021-06-15","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-02","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}