Immune effector cell–associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations
Blood, vol. 142, pp. 865–877
Abstract
Hematological toxicity is the most common adverse event after chimeric antigen receptor (CAR) T-cell therapy. Cytopenias can be profound and long-lasting and can predispose for severe infectious complications. In a recent worldwide survey, we demonstrated that there remains considerable heterogeneity in regard to current practice patterns. Here, we sought to build consensus on the grading and management of immune effector cell-associated hematotoxicity (ICAHT) after CAR T-cell therapy. For this purpose, a joint effort between the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA) involved an international panel of 36 CAR T-cell experts who met in a series of virtual conferences, culminating in a 2-day meeting in Lille, France. On the basis of these deliberations, best practice recommendations were developed. For the grading of ICAHT, a classification system based on depth and duration of neutropenia was developed for early (day 0-30) and late (after day +30) cytopenia. Detailed recommendations on risk factors, available preinfusion scoring systems (eg, CAR-HEMATOTOX score), and diagnostic workup are provided. A further section focuses on identifying hemophagocytosis in the context of severe hematotoxicity. Finally, we review current evidence and provide consensus recommendations for the management of ICAHT, including growth factor support, anti-infectious prophylaxis, transfusions, autologous hematopoietic stem cell boost, and allogeneic hematopoietic cell transplantation. In conclusion, we propose ICAHT as a novel toxicity category after immune effector cell therapy, provide a framework for its grading, review literature on risk factors, and outline expert recommendations for the diagnostic workup and short- and long-term management.
Authors 37
-
LMU Klinikum · Ludwig-Maximilians-Universität München
Affiliation as printed
1Department of Medicine III, LMU University Hospital, LMU Munich, Munich, Germany
-
Marion Subklewe corresponding
LMU Klinikum · Ludwig-Maximilians-Universität München
Affiliation as printed
1Department of Medicine III, LMU University Hospital, LMU Munich, Munich, Germany
-
King Faisal Specialist Hospital & Research Centre
Affiliation as printed
2Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
-
Lyon 1 Université · Hospices Civils de Lyon
Affiliation as printed
3Department of Hematology, Hospices Civils de Lyon and Université Claude Bernard Lyon 1, Lyon, France
-
Affiliation as printed
4Pediatric Transplantation Unit, Department of Medicine and Surgery, University of Milan-Bicocca-Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
-
Universitat Autònoma de Barcelona · Vall d'Hebron Hospital Universitari · Vall d'Hebron Institute of Oncology
Affiliation as printed
5Department of Hematology, Vall d’Hebron University Hospital, Experimental Hematology, Vall d’Hebron Institute of Oncology, Barcelona, Spain
6Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
-
Affiliation as printed
7Division of Hematology and Cell Therapy Unit, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
-
Affiliation as printed
8School of Cancer & Pharmaceutical Sciences, King’s College London, London, United Kingdom
-
IRCCS Ospedale San Raffaele · Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
Affiliation as printed
9Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Hospital, Milan, Italy
-
Inserm · Aix-Marseille Université · Centre de Recherche en Cancérologie de Marseille · Institut Paoli-Calmettes
Affiliation as printed
10Institut Paoli-Calmettes Comprehensive Cancer Centre and Module Biothérapies du Centre d’Investigations Cliniques de Marseille, INSERM–Aix-Marseille Université–AP-HM–IPC, CBT-1409, Marseille, France
-
IRCCS Ospedale San Raffaele · Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
Affiliation as printed
9Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Hospital, Milan, Italy
-
University of Milan · Fondazione IRCCS Istituto Nazionale dei Tumori
Affiliation as printed
11Division of Hematology and Stem Cell Transplantation, Fondazione IRCCS Instituto Nazionale dei Tumori, University of Milan, Milan, Italy
-
Affiliation as printed
12Oncoimmunotherapy Unit, Department of Hematology, Hospital Clinic de Barcelona, Barcelona, Spain
-
Université Paris Cité · Assistance Publique – Hôpitaux de Paris
Affiliation as printed
13Université de Paris, Assistance Publique–Hopitaux de Paris, Service d’hémato-oncologie, Paris, France
-
IRCCS Ospedale San Raffaele · Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
Affiliation as printed
9Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Hospital, Milan, Italy
-
Inserm · Centre Hospitalier Universitaire de Rennes · Microenvironment and B-cells: Immunopathology, Cell, Differentiation and Cancer · Université de Rennes
Affiliation as printed
14Department of Hematology, CHU Rennes, University of Rennes, INSERM U1236, Rennes, France
-
Universitat Autònoma de Barcelona · Vall d'Hebron Hospital Universitari · Vall d'Hebron Institute of Oncology
Affiliation as printed
5Department of Hematology, Vall d’Hebron University Hospital, Experimental Hematology, Vall d’Hebron Institute of Oncology, Barcelona, Spain
6Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
Department of Hematology, Vall d'Hebron University Hospital, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain, Barcelona, Spain
-
Affiliation as printed
15Department of Medicine I, Medical University of Vienna, Vienna, Austria
-
Amsterdam University Medical Centers
Affiliation as printed
16Department of Hematology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
-
Karolinska University Hospital · Karolinska Institutet
Affiliation as printed
17Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Department of Laboratory Medicine and Medicine Huddinge, Karolinska University Hospital and Institute, Stockholm, Sweden
-
Tel Aviv University · Sheba Medical Center
Affiliation as printed
18Division of Hematology, Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer, Israel
Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel, Tel-Hashomer, Israel, Israel
-
University of Milan · Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Affiliation as printed
19Hematology and Bone Marrow Transplantation Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
-
University Hospital Centre Zagreb
Affiliation as printed
20Department of Hematology, University Hospital Centre Zagreb, Zagreb, Croatia
-
University College Hospital · University College London Hospitals NHS Foundation Trust · University College London
Affiliation as printed
21Department of Hematology, University College London Hospital, London, United Kingdom
-
IRCCS Ospedale San Raffaele · Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
Affiliation as printed
9Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Hospital, Milan, Italy
-
Universidad de Salamanca · Instituto de Investigación Biomédica de Salamanca
Affiliation as printed
22University of Salamanca, IBSAL-University Hospital of Salamanca, Salamanca, Spain
-
European Society for Blood and Marrow Transplantation · European Society for Blood and Marrow Transplantation
Affiliation as printed
23Executive Office, European Society for Blood and Marrow Transplantation, Barcelona, Spain
-
University of Zurich · University Hospital Zurich
Affiliation as printed
24Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland
-
University Hospital Heidelberg
Affiliation as printed
25Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany
-
Sheffield Teaching Hospitals NHS Foundation Trust
Affiliation as printed
26Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
-
Université Paris Cité · Assistance Publique – Hôpitaux de Paris
Affiliation as printed
13Université de Paris, Assistance Publique–Hopitaux de Paris, Service d’hémato-oncologie, Paris, France
-
Affiliation as printed
27Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany
-
Istituto di Ematologia di Bologna · University of Bologna
Affiliation as printed
28IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli,” Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy
-
Queen Mary University of London · Barts Cancer Institute
Affiliation as printed
29Barts Cancer Institute, Queen Mary, University of London, London, United Kingdom
-
Vita-Salute San Raffaele University · IRCCS Ospedale San Raffaele
Affiliation as printed
30Division of Immunology, Transplantation and Infectious Disease, Experimental Hematology Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
-
Affiliation as printed
31Clinical Hematology Department, Institut Català d’Oncologia-L’Hospitalet, Barcelona, Spain
-
Inserm · Université de Lille · Centre Hospitalier Universitaire de Lille · Institute for Translational Research in Inflammation
Affiliation as printed
32CHU de Lille, University of Lille, INSERM U1286, Infinite, Lille, France
Cited by 354 stored of 355
Cited by patents worldwide 1 (Lens.org)
-
MARKERS FOR PREDICTION OF ADVERSE OUTCOMES OF CAR-T THERAPYWO2026078233A2 2026-04-16 Pending