{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T02:15:05Z","timestamp":1794363305472,"version":"4.9.0"},"reference-count":56,"publisher":"American Society of Hematology","issue":"24","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hematotoxicity represents a frequent chimeric antigen receptor (CAR) T-cell\u2013related adverse event and remains poorly understood. In this multicenter analysis, we studied patterns of hematopoietic reconstitution and evaluated potential predictive markers in 258 patients receiving axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) for relapsed\/refractory large B-cell lymphoma. We observed profound (absolute neutrophil count [ANC] &amp;lt;100 cells per \u00b5L) neutropenia in 72% of patients and prolonged (21 days or longer) neutropenia in 64% of patients. The median duration of severe neutropenia (ANC &amp;lt; 500 cells per \u00b5L) was 9 days. We aimed to identify predictive biomarkers of hematotoxicity using the duration of severe neutropenia until day +60 as the primary end point. In the training cohort (n\u2009=\u200958), we observed a significant correlation with baseline thrombocytopenia (r\u2009=\u2009\u22120.43; P\u2009=\u2009.001) and hyperferritinemia (r\u2009=\u20090.54; P\u2009&amp;lt;\u2009.0001) on univariate and multivariate analysis. Incidence and severity of cytokine-release syndrome, immune effector cell\u2013associated neurotoxicity syndrome, and peak cytokine levels were not associated with the primary end point. We created the CAR-HEMATOTOX model, which included markers associated with hematopoietic reserve (eg, platelet count, hemoglobin, and ANC) and baseline inflammation (eg, C-reactive protein and ferritin). This model was validated in independent cohorts, one from Europe (n\u2009=\u200991) and one from the United States (n\u2009=\u2009109) and discriminated patients with severe neutropenia \u226514 days to &amp;lt;14 days (pooled validation: area under the curve, 0.89; sensitivity, 89%; specificity, 68%). A high CAR-HEMATOTOX score resulted in a longer duration of neutropenia (12 vs 5.5 days; P &amp;lt; .001) and a higher incidence of severe thrombocytopenia (87% vs 34%; P &amp;lt; .001) and anemia (96% vs 40%; P &amp;lt; .001). The score implicates bone marrow reserve and inflammation prior to CAR T-cell therapy as key features associated with delayed cytopenia and will be useful for risk-adapted management of hematotoxicity.<\/jats:p>","DOI":"10.1182\/blood.2020010543","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T23:07:55Z","timestamp":1625094475000},"page":"2499-2513","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":489,"title":["CAR-HEMATOTOX: a model for CAR T-cell\u2013related hematologic toxicity in relapsed\/refractory large B-cell lymphoma"],"prefix":"10.1182","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3905-0251","authenticated-orcid":false,"given":"Kai","family":"Rejeski","sequence":"first","affiliation":[{"name":"Department of Medicine III, University Hospital, Ludwig Maximilian University (LMU) Munich, Munich, Germany;"},{"name":"Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany;"},{"name":"German Cancer Consortium, Munich Site, and German Cancer Research Center, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Sesques","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Universit\u00e9 Claude Bernard Lyon 1, INSERM 1052, Pierre-B\u00e9nite, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0749-1389","authenticated-orcid":false,"given":"Eva","family":"Hoster","sequence":"additional","affiliation":[{"name":"Department of Medicine III, University Hospital, Ludwig Maximilian University (LMU) Munich, Munich, Germany;"},{"name":"Institute for Medical Informatics, 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