{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:26:32Z","timestamp":1793499992274,"version":"4.5.0"},"reference-count":43,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2022,4,6]]},"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) represents a promising treatment modality for an increasing number of B-cell malignancies. However, prolonged cytopenias and infections substantially contribute to the toxicity burden of CAR-T. The recently developed CAR-HEMATOTOX (HT) score\u2014composed of five pre-lymphodepletion variables (eg, absolute neutrophil count, platelet count, hemoglobin, C-reactive protein, ferritin)\u2014enables risk stratification of hematological toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multicenter retrospective analysis, we characterized early infection events (days 0\u201390) and clinical outcomes in 248 patients receiving standard-of-care CD19 CAR-T for relapsed\/refractory large B-cell lymphoma. This included a derivation cohort (cohort A, 179 patients) and a second independent validation cohort (cohort B, 69 patients). Cumulative incidence curves were calculated for all-grade, grade \u22653, and specific infection subtypes. Clinical outcomes were studied via Kaplan-Meier estimates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In a multivariate analysis adjusted for other baseline features, the HT score identified patients at high risk for severe infections (adjusted HR 6.4, 95% CI 3.1 to 13.1). HT\n                      <jats:sup>high<\/jats:sup>\n                      patients more frequently developed severe infections (40% vs 8%, p&lt;0.0001)\u2014particularly severe bacterial infections (27% vs 0.9%, p&lt;0.0001). Additionally, multivariate analysis of post-CAR-T factors revealed that infection risk was increased by prolonged neutropenia (\u226514 days) and corticosteroid use (\u22659 days), and decreased with fluoroquinolone prophylaxis. Antibacterial prophylaxis significantly reduced the likelihood of severe bacterial infections in HT\n                      <jats:sup>high<\/jats:sup>\n                      (16% vs 46%, p&lt;0.001), but not HT\n                      <jats:sup>low<\/jats:sup>\n                      patients (0% vs 2%, p=n.s.). Collectively, HT\n                      <jats:sup>high<\/jats:sup>\n                      patients experienced worse median progression-free (3.4 vs 12.6 months) and overall survival (9.1 months vs not-reached), and were hospitalized longer (median 20 vs 16 days). Severe infections represented the most common cause of non-relapse mortality after CAR-T and were associated with poor survival outcomes. A trend toward increased non-relapse mortality in HT\n                      <jats:sup>high<\/jats:sup>\n                      patients was observed (8.0% vs 3.7%, p=0.09).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These data demonstrate the utility of the HT score to risk-stratify patients for infectious complications and poor survival outcomes\n                      <jats:italic>prior<\/jats:italic>\n                      to CD19 CAR-T. High-risk patients likely benefit from anti-infective prophylaxis and should be closely monitored for potential infections and relapse.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2021-004475","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T13:40:23Z","timestamp":1653313223000},"page":"e004475","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":193,"title":["The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R\/R LBCL"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3905-0251","authenticated-orcid":false,"given":"Kai","family":"Rejeski","sequence":"first","affiliation":[{"name":"Department of Medicine III, Hematology and Oncology, University Hospital, LMU Munich, Munich, Germany"},{"name":"Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany"},{"name":"German Cancer Consortium (DKTK) 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, Florida, USA"},{"name":"Blood & Marrow Transplant Program, Miami Cancer Institute, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Iacoboni","sequence":"additional","affiliation":[{"name":"Department of Hematology, Vall d\u2019Hebron Institute of Oncology (VHIO), University Hospital Vall d\u2019Hebron, Universitat Aut\u00f2noma of Barcelona (UAB), Department of Medicin, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Penack","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Tumorimmunology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"German Cancer Consortium (DKTK) Berlin Site, and German Cancer Research Center, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veit","family":"B\u00fccklein","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Hematology and Oncology, University Hospital, LMU Munich, Munich, Germany"},{"name":"Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liv","family":"Jentzsch","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Mougiakakos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 5, Hematology and Oncology, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Johnson","sequence":"additional","affiliation":[{"name":"USF Morsani College of Medicine, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Arciola","sequence":"additional","affiliation":[{"name":"USF Morsani College of Medicine, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Carpio","sequence":"additional","affiliation":[{"name":"Department of Hematology, Vall d\u2019Hebron Institute of Oncology (VHIO), University Hospital Vall d\u2019Hebron, Universitat Aut\u00f2noma of Barcelona (UAB), Department of Medicin, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"Blumenberg","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Hematology and Oncology, University Hospital, LMU Munich, Munich, Germany"},{"name":"Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Hoster","sequence":"additional","affiliation":[{"name":"Institute for Medical Information Processing, Biometry and Epidemiology (IBE), LMU Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Bullinger","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Tumorimmunology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"German Cancer Consortium (DKTK) Berlin Site, and German Cancer Research Center, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick L","family":"Locke","sequence":"additional","affiliation":[{"name":"Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"von Bergwelt-Baildon","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Hematology and Oncology, University Hospital, LMU Munich, Munich, Germany"},{"name":"German Cancer Consortium (DKTK) Munich Site, and German Cancer Research Center, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Mackensen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 5, Hematology and Oncology, University of Erlangen-Nuremberg, Erlangen, 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Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma. 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