{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:54:44Z","timestamp":1793840084100,"version":"4.6.1"},"reference-count":26,"publisher":"American Society of Hematology","issue":"17","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Patients who develop chimeric antigen receptor (CAR) T-cell\u2013related severe cytokine release syndrome (CRS) and immune effector cell\u2013associated neurotoxicity syndrome (ICANS) exhibit hemodynamic instability and endothelial activation. The EASIX (Endothelial Activation and Stress Index) score (lactate dehydrogenase [LDH; U\/L] \u00d7 creatinine [mg\/dL]\/platelets [PLTs; 109 cells\/L]) is a marker of endothelial damage that correlates with outcomes in allogeneic hematopoietic cell transplantation. Elevated LDH and low PLTs have been associated with severe CRS and ICANS, as has C-reactive protein (CRP), while increased creatinine is seen only in a minority of advanced severe CRS cases. We hypothesized that EASIX and 2 new modified EASIX formulas (simplified EASIX, which excludes creatinine, and modified EASIX [m-EASIX], which replaces creatinine with CRP [mg\/dL]), calculated peri-CAR T-cell infusion, would be associated with development of severe (grade \u2265 3) CRS and ICANS. We included 118 adults, 53 with B-acute lymphoblastic leukemia treated with 1928z CAR T cells (NCT01044069) and 65 with diffuse large B-cell lymphoma treated with axicabtagene ciloleucel or tisagenlecleucel. The 3 formulas showed similar predictive power for severe CRS and ICANS. However, low PLTs and high CRP values were the only variables individually correlated with these toxicities. Moreover, only m-EASIX was a significant predictor of disease response. m-EASIX could discriminate patients who subsequently developed severe CRS preceding the onset of severe symptoms (area under the curve [AUC] at lymphodepletion, 80.4%; at day \u22121, 73.0%; and at day +1, 75.4%). At day +3, it also had high discriminatory ability for severe ICANS (AUC, 73%). We propose m-EASIX as a clinical tool to potentially guide individualized management of patients at higher risk for severe CAR T-cell\u2013related toxicities.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020003885","type":"journal-article","created":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T16:57:25Z","timestamp":1629910645000},"page":"3397-3406","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":218,"title":["Modified EASIX predicts severe cytokine release syndrome and neurotoxicity after chimeric antigen receptor T cells"],"prefix":"10.1182","volume":"5","author":[{"given":"Martina","family":"Pennisi","sequence":"first","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"},{"name":"Hematology Service, Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Sanchez-Escamilla","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"},{"name":"Department of Hematology, University Hospital Marqu\u00e9s de Valdecilla \u2013 IDIVAL, Santander, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8310-6684","authenticated-orcid":false,"given":"Jessica R.","family":"Flynn","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roni","family":"Shouval","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6290-1061","authenticated-orcid":false,"given":"Ana","family":"Alarcon Tomas","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari Lynn","family":"Silverberg","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9036-9463","authenticated-orcid":false,"given":"Connie","family":"Batlevi","sequence":"additional","affiliation":[{"name":"Lymphoma Service, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renier J.","family":"Brentjens","sequence":"additional","affiliation":[{"name":"Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0794-3226","authenticated-orcid":false,"given":"Parastoo B.","family":"Dahi","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M.","family":"Devlin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Diamonte","sequence":"additional","affiliation":[{"name":"Cellular Therapeutics Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1944-5053","authenticated-orcid":false,"given":"Sergio","family":"Giralt","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth F.","family":"Halton","sequence":"additional","affiliation":[{"name":"Cellular Therapeutics Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-773X","authenticated-orcid":false,"given":"Tania","family":"Jain","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Maloy","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Mead","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Lia","family":"Palomba","sequence":"additional","affiliation":[{"name":"Lymphoma Service, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josel","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Santomasso","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig S.","family":"Sauter","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Scordo","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9977-0456","authenticated-orcid":false,"given":"Gunjan L.","family":"Shah","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae H.","family":"Park","sequence":"additional","affiliation":[{"name":"Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9925-3048","authenticated-orcid":false,"given":"Lucrecia","family":"Yanez San Segundo","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"},{"name":"Department of Hematology, University Hospital Marqu\u00e9s de Valdecilla \u2013 IDIVAL, Santander, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5910-4571","authenticated-orcid":false,"given":"Miguel-Angel","family":"Perales","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"issue":"9","key":"2021090715280050700_B1","doi-asserted-by":"crossref","first-page":"e414","DOI":"10.1016\/S2352-3026(17)30108-4","article-title":"EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis","volume":"4","author":"Luft","year":"2017","journal-title":"Lancet Haematol."},{"issue":"5","key":"2021090715280050700_B2","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.bbmt.2020.01.028","article-title":"Endothelial Activation and Stress Index (EASIX) at admission predicts fluid overload in recipients of allogeneic stem cell transplantation","volume":"26","author":"Varma","year":"2020","journal-title":"Biol Blood Marrow Transplant."},{"issue":"3","key":"2021090715280050700_B3","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/s41409-019-0703-1","article-title":"EASIX and mortality after allogeneic stem cell transplantation","volume":"55","author":"Luft","year":"2020","journal-title":"Bone Marrow Transplant."},{"issue":"12","key":"2021090715280050700_B4","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1182\/bloodadvances.2019032268","article-title":"External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell 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