{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:04:38Z","timestamp":1794002678437,"version":"4.8.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:00:00Z","timestamp":1696291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>CAR-T cell therapy is a novel approach in the treatment of hematological tumors. However, it is associated with life-threatening side effects, such as the severe cytokine release syndrome (sCRS). Therefore, predicting the occurrence and development of sCRS is of great significance for clinical CAR-T therapy. The study of existing clinical data by artificial intelligence may bring useful information.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>By analyzing the heat map of clinical factors and comparing them between severe and non-severe CRS, we can identify significant differences among these factors and understand their interrelationships. Ultimately, a decision tree approach was employed to predict the timing of severe CRS in both children and adults, considering variables such as the same day, the day before, and initial values.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We measured cytokines and clinical biomarkers in 202 patients who received CAR-T therapy. Peak levels of 25 clinical factors, including IFN-\u03b3, IL6, IL10, ferritin, and D-dimer, were highly associated with severe CRS after CAR T cell infusion. Using the decision tree model, we were able to accurately predict which patients would develop severe CRS consisting of three clinical factors, classified as same-day, day-ahead, and initial value prediction. Changes in serum biomarkers, including C-reactive protein and ferritin, were associated with CRS, but did not alone predict the development of severe CRS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our research will provide significant information for the timely prevention and treatment of sCRS, during CAR-T immunotherapy for tumors, which is essential to reduce the mortality rate of patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2023.1273507","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T03:46:56Z","timestamp":1696304816000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["Prediction of severe CRS and determination of biomarkers in B cell-acute lymphoblastic leukemia treated with CAR-T cells"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhenyu","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengkui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0564-6","article-title":"Clinical lessons learned from the first leg of the CAR T cell journey","volume":"25","author":"Majzner","year":"2019","journal-title":"Nat Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1056\/NEJMra1706169","article-title":"Chimeric antigen receptor therapy","volume":"379","author":"June","year":"2018","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709919","article-title":"Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia","volume":"378","author":"Park","year":"2018","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61403-3","article-title":"T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial","volume":"385","author":"Lee","year":"2015","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.611366","article-title":"Characteristics and Risk Factors of Cytokine Release Syndrome in Chimeric Antigen Receptor T Cell Treatment","volume":"12","author":"Yan","year":"2021","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.bbmt.2019.08.003","article-title":"Late events after treatment with CD19-targeted chimeric antigen receptor modified T cells","volume":"26","author":"Cordeiro","year":"2020","journal-title":"Biol Blood Marrow Transplant"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000186","article-title":"CAR T cell toxicity: current management and future directions","volume":"3","author":"Yanez","year":"2019","journal-title":"Hemasphere"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000035","article-title":"Managing cytokine release syndrome associated with novel T cell-engaging therapies","volume":"20","author":"Maude SL","year":"2014","journal-title":"Cancer J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.627764","article-title":"Biomarkers for chimeric antigen receptor T cell therapy in acute lymphoblastic leukemia: prospects for personalized management and prognostic prediction","volume":"12","author":"Hong","year":"2021","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s40364-018-0116-0","article-title":"Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy","volume":"6","author":"Wang","year":"2018","journal-title":"biomark Res"},{"key":"B12","doi-asserted-by":"publisher","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"},{"key":"B13","doi-asserted-by":"publisher","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"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21423","article-title":"Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis","volume":"50","author":"Allen","year":"2008","journal-title":"Pediatr Blood Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e31824227b9","article-title":"Serum ferritin is a cost-effective laboratory marker for hemophagocytic lymphohistiocytosis in the developing world","volume":"2012","author":"Switala JR","year":"2012","journal-title":"J Pediatr Hematol Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s40364-020-00190-8","article-title":"Biomarkers in individualized management of chimeric antigen receptor T cell therapy","volume":"8","author":"Du","year":"2020","journal-title":"biomark Res"},{"key":"B17","doi-asserted-by":"publisher","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":"B18","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac5415","article-title":"Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia","volume":"7","author":"Porter","year":"2015","journal-title":"Sci Transl Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14680","article-title":"Neurological toxicities and coagulation disorders in the cytokine release syndrome during CAR-T therapy","volume":"181","author":"Mei","year":"2018","journal-title":"Br J Haematol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-883710","article-title":"Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy","volume":"133","author":"Hay","year":"2019","journal-title":"Blood"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25108","article-title":"Potent anti-leukemia activities of humanized CD19-targeted Chimeric antigen receptor T (CAR-T) cells in patients with relapsed\/refractory acute lymphoblastic leukemia","volume":"93","author":"Cao","year":"2018","journal-title":"Am J Hematol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3888","article-title":"Dissecting the tumor-immune landscape in chimeric antigen receptor T-cell therapy: key challenges and opportunities for a systems immunology approach","volume":"26","author":"Chen","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"67","DOI":"10.3324\/haematol.11575","article-title":"Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model","volume":"93","author":"Montesinos","year":"2008","journal-title":"Haematologica"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1365-2141.2004.05094.x","article-title":"Tumour lysis syndrome: new therapeutic strategies and classification","volume":"127","author":"Cairo","year":"2004","journal-title":"Br J Haematol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000002053","article-title":"Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia","volume":"45","author":"Fitzgerald","year":"2017","journal-title":"Crit Care Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1799","article-title":"Potent anti-leukemia activities of chimeric antigen receptor-Modified T cells against CD19 in chinese patients with relapsed\/Refractory acute lymphocytic leukemia","volume":"23","author":"Hu","year":"2017","journal-title":"Clin Cancer Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-793141","article-title":"Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy","volume":"130","author":"Hay","year":"2017","journal-title":"Blood"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-019-03685-z","article-title":"Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy","volume":"98","author":"Jiang","year":"2019","journal-title":"Ann Hematol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.11.027","article-title":"Coagulation disorders after chimeric antigen receptor T cell therapy: analysis of 100 patients with relapsed and refractory hematologic Malignancies","volume":"26","author":"Wang","year":"2020","journal-title":"Biol Blood Marrow Transplant"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407222","article-title":"Chimeric antigen receptor T cells for sustained remissions in leukemia","volume":"371","author":"Maude","year":"2014","journal-title":"N Engl J Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85309","article-title":"CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients","volume":"126","author":"Turtle","year":"2016","journal-title":"J Clin Invest"},{"key":"B32","doi-asserted-by":"publisher","first-page":"224ra225","DOI":"10.1126\/scitranslmed.3008226","article-title":"Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia","volume":"6","author":"Davila","year":"2014","journal-title":"Sci Transl Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-immunol-031210-101312","article-title":"Regulation and functions of the IL-10 family of cytokines in inflammation and disease","volume":"29","author":"Ouyang","year":"2011","journal-title":"Annu Rev Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s00281-011-0290-8","article-title":"Fibrinogen as a key regulator of inflammation in disease","volume":"34","author":"Davalos","year":"2012","journal-title":"Semin Immunopathol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.21037\/jtd.2019.11.63","article-title":"Role of procalcitonin use in the management of sepsis","volume":"12","author":"Gregoriano","year":"2020","journal-title":"J Thorac Dis"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/ncp.10588","article-title":"The use of visceral proteins as nutrition markers: an ASPEN position paper","volume":"36","author":"Evans","year":"2021","journal-title":"Nutr Clin Pract"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1159\/000495946","article-title":"Utility of cardiac biomarkers in the setting of kidney disease","volume":"141","author":"Savoj","year":"2019","journal-title":"Nephron"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2017.11.026","article-title":"Gamma-glutamyl transferase and the risk of atherosclerosis and coronary heart disease","volume":"476","author":"Ndrepepa","year":"2018","journal-title":"Clin Chim Acta"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1177\/0300060518764717","article-title":"Assessment of clinical sepsis-associated biomarkers in a septic mouse model","volume":"46","author":"Li","year":"2018","journal-title":"J Int Med Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14975","article-title":"Coagulopathy in COVID-19","volume":"18","author":"Iba","year":"2020","journal-title":"J Thromb Haemost"},{"key":"B41","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.blre.2018.11.002","article-title":"Recent advances in CAR T-cell toxicity: Mechanisms","volume":"34","author":"Brudno","year":"2019","journal-title":"Manifestations Manage"},{"key":"B42","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/nrclinonc.2018.19","article-title":"Toxicity management after chimeric antigen receptor T cell therapy: one size does not fit 'ALL'","volume":"15","author":"Teachey","year":"2018","journal-title":"Nat Rev Clin Oncol"}],"updated-by":[{"DOI":"10.3389\/fimmu.2024.1379325","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000}}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1273507\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T10:08:22Z","timestamp":1707386902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1273507\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,3]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2023.1273507"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1273507","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,3]]},"article-number":"1273507"}}