{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T08:10:55Z","timestamp":1794471055735,"version":"4.9.1"},"reference-count":12,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"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":[[2023,3,23]]},"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:p>We investigated the incidence and outcome of anti-CD19 chimeric antigen receptor (CAR) T-cells-associated Common Terminology Criteria for Adverse Events (CTCAE) \u2265grade 3 cytopenia. In the EBMT CAR-T registry, we identified 398 adult patients with large B-cell lymphoma who had been treated with CAR-T-cells with axicel (62%) or tisacel (38%) before August 2021 and had cytopenia status documented for the first 100 days. Most patients had received two or three previous lines of therapy, however, 22.3% had received four or more. Disease status was progressive in 80.4%, stable in 5.0% and partial\/complete remission in 14.6%. 25.9% of the patients had received a transplantation before. Median age was 61.4 years (min\u2013max; IQR=18.7\u201381; (52.9\u201369.5)).<\/jats:p>\n               <jats:p>The cumulative incidence of \u2265grade 3 cytopenia was 9.0% at 30 days (95% CI (6.5 to 12.1)) and 12.1% at 100 days after CAR T-cell infusion (95% CI (9.1 to 15.5)). The median time from CAR-T infusion to cytopenia onset was 16.5 days (min\u2013max; IQR=1\u201390; (4\u201329.8)). Grade 3 and grade 4 CTCAE cytopenia occurred in 15.2% and 84.8%, respectively. In 47.6% there was no resolution.<\/jats:p>\n               <jats:p>Severe cytopenia had no significant impact on overall survival (OS) (HR 1.13 (95% CI 0.74 to 1.73), p=0.57). However, patients with severe cytopenia had a poorer progression-free survival (PFS) (HR 1.54 (95% CI 1.07 to 2.22), p=0.02) and a higher relapse incidence (HR 1.52 (95% CI 1.04 to 2.23), p=0.03). In those patients who developed severe cytopenia during the first 100 days (n=47), OS, PFS, relapse incidence and non-relapse mortality at 12 months after diagnosis of severe cytopenia were 53.6% (95%\u2009CI (40.3 to 71.2)), 20% (95% CI (10.4 to 38.6)), 73.5% (95% CI (55.2 to 85.2)) and 6.5% (95% CI (1.7 to 16.2)), respectively.<\/jats:p>\n               <jats:p>In multivariate analysis of severe cytopenia risk factors, only year of CAR-T infusion (HR=0.61, 95% CI (0.39 to 0.95), p=0.028) and total number of treatment lines before CAR-T infusion (one or two lines vs three or more, HR=0.41, 95% CI (0.21 to 0.83), p=0.013) had a significant positive association with the incidence of cytopenia. Other factors, such as previous transplantation, disease status at time of CAR-T, patient age and patient sex, had no significant association.<\/jats:p>\n               <jats:p>Our data provide insight on frequency and clinical relevance of severe cytopenia after CAR T-cell therapy in the European real-world setting.<\/jats:p>","DOI":"10.1136\/jitc-2022-006406","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T22:45:58Z","timestamp":1681857958000},"page":"e006406","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4876-802X","authenticated-orcid":false,"given":"Olaf","family":"Penack","sequence":"first","affiliation":[{"name":"Medical Clinic, Department for Haematology, Oncology and Tumorimmunology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"},{"name":"EBMT Transplant Complications Working Party, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Peczynski","sequence":"additional","affiliation":[{"name":"EBMT Transplant Complications Working Party, Paris, France"},{"name":"EBMT Paris study office; Department of Haematology, Saint Antoine Hospital; INSERM UMR-S 938, Sorbonne University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Koenecke","sequence":"additional","affiliation":[{"name":"EBMT Transplant Complications Working Party, Paris, France"},{"name":"Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Polge","sequence":"additional","affiliation":[{"name":"EBMT Transplant Complications Working Party, Paris, France"},{"name":"EBMT Paris study office; Department of Haematology, Saint Antoine Hospital; INSERM UMR-S 938, Sorbonne University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Kuhnl","sequence":"additional","affiliation":[{"name":"Departement of Haematological Medicine, Kings College Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Fegueux","sequence":"additional","affiliation":[{"name":"D\u00e9partement d'H\u00e9matologie Clinique, CHU Lapeyronie, Montpellier, Languedoc-Roussillon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Daskalakis","sequence":"additional","affiliation":[{"name":"Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaus","family":"Kr\u00f6ger","sequence":"additional","affiliation":[{"name":"University Hospital Eppendorf, Bone Marrow Transplantation Centre, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dreger","sequence":"additional","affiliation":[{"name":"University of Heidelberg, Medizinische Klinik u. Poliklinik V, Heidelberg, Germany"},{"name":"Department of Hematology, Oncology and Internal Medicine, the Medical University of Warsaw, Marseille, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Besley","sequence":"additional","affiliation":[{"name":"Departement of Paediatric Oncology\/BMT, Bristol Royal Hospital for Children, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"Schanz","sequence":"additional","affiliation":[{"name":"University Hospital, Clinic of Hematology, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Bloor","sequence":"additional","affiliation":[{"name":"Christie NHS Trust Hospital, Adult Leukaemia and Bone Marrow Transplant Unit, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Ganser","sequence":"additional","affiliation":[{"name":"Department of Haematology, Hemostasis, Oncology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edouard","family":"Forcade","sequence":"additional","affiliation":[{"name":"CHU Bordeaux, H\u00f4pital Haut-leveque, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia L\u00f3pez","family":"Corral","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico, Servicio de Hematolog\u00eda, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob R","family":"Passweg","sequence":"additional","affiliation":[{"name":"University Hospital, Hematology, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urban","family":"Novak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Bern University Hospital, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Moiseev","sequence":"additional","affiliation":[{"name":"EBMT Transplant Complications Working Party, Paris, France"},{"name":"First Pavlov State Medical University of St Petersburg, St Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Schoemans","sequence":"additional","affiliation":[{"name":"EBMT Transplant Complications Working Party, Paris, France"},{"name":"Department of Hematology, University Hospitals Leuven and KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz W","family":"Basak","sequence":"additional","affiliation":[{"name":"EBMT Transplant Complications Working Party, Paris, France"},{"name":"Department of Hematology, Oncology and Internal Medicine, the Medical University of Warsaw, Marseille, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3755-4889","authenticated-orcid":false,"given":"Christian","family":"Chabannon","sequence":"additional","affiliation":[{"name":"EBMT Cellular Therapy and Immunobiology Working Party, Leiden, The Netherlands"},{"name":"Institut Paoli-Calmettes Comprehensive Cancer Centre, Inserm CBT-1409, Aix-Marseille Universit\u00e9, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sureda","sequence":"additional","affiliation":[{"name":"Clinical Hematology Department, Institut Catal\u00e0 d'Oncologia-Hospitalet, Institut de Ci\u00e8ncies Biom\u00e8diques de Bellvitge (IDIBELL), Universitat de Barcelona, Barcelona 08908, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Averbuch","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Pediatric Infectious Diseases, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel"},{"name":"EBMT Infectious Diseases Working Party"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Tumor Immunology, Helios Klinikum Berlin-Buch, Berlin, Germany"},{"name":"EBMT Lymphoma Working Party"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8189-5779","authenticated-orcid":false,"given":"Rafael","family":"de la Camara","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Pediatric Infectious Diseases, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel"},{"name":"Department of Haematology, Hospital Universitario de la Princesa, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinaida","family":"Peric","sequence":"additional","affiliation":[{"name":"EBMT Transplant Complications Working Party, Paris, France"},{"name":"University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"2025100301525841000_11.4.e006406.1","first-page":"349","article-title":"GLA\/DRST real-world outcome analysis of car T-cell therapies for large B-cell lymphoma in Germany","volume":"140","author":"Bethge","year":"2022","journal-title":"Blood"},{"key":"2025100301525841000_11.4.e006406.2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020010543"},{"key":"2025100301525841000_11.4.e006406.3","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1182\/bloodadvances.2022008042","article-title":"Hematopoietic stem cell boost for persistent neutropenia after car T-cell therapy: a GLA\/DRST study","volume":"7","author":"Gagelmann","year":"2023","journal-title":"Blood 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Common terminology criteria for adverse events (CTCAE) version 5.0. 2017. Available: https.ctep.cancer.gov\/protocolDevelopment\/electronic_applicatio ns\/ctc.htm"},{"key":"2025100301525841000_11.4.e006406.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31366-0"},{"key":"2025100301525841000_11.4.e006406.8","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.3324\/haematol.2020.254045","article-title":"Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma","volume":"106","author":"Strati","year":"2021","journal-title":"Haematologica"},{"key":"2025100301525841000_11.4.e006406.9","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002509"},{"key":"2025100301525841000_11.4.e006406.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2116133"},{"key":"2025100301525841000_11.4.e006406.11","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1080\/10428194.2022.2056172","article-title":"Acute and delayed cytopenias following CAR T-cell therapy: an investigation of risk factors and mechanisms","volume":"63","author":"Brudno","year":"2022","journal-title":"Leuk Lymphoma"},{"key":"2025100301525841000_11.4.e006406.12","doi-asserted-by":"crossref","DOI":"10.3390\/cancers14061501","article-title":"Cytopenia after CAR-T cell therapy-A brief review of A complex problem","volume":"14","author":"Sharma","year":"2022","journal-title":"Cancers (Basel)"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2022-006406","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T08:53:02Z","timestamp":1759481582000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2022-006406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":12,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4,18]]},"published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1136\/jitc-2022-006406"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2022-006406","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4]]}}}