Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for hematologic malignancies. However, it is frequently complicated by immune effector cell-associated hematotoxicity (ICAHT), a potentially life-threatening adverse event encompassing neutropenia, anemia, and th...

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Main Authors: Ofrat Beyar-Katz, Kai Rejeski, Roni Shouval
Format: Article
Language:English
Published: Ferrata Storti Foundation 2025-02-01
Series:Haematologica
Online Access:https://haematologica.org/article/view/11947
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author Ofrat Beyar-Katz
Kai Rejeski
Roni Shouval
author_facet Ofrat Beyar-Katz
Kai Rejeski
Roni Shouval
author_sort Ofrat Beyar-Katz
collection DOAJ
description Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for hematologic malignancies. However, it is frequently complicated by immune effector cell-associated hematotoxicity (ICAHT), a potentially life-threatening adverse event encompassing neutropenia, anemia, and thrombocytopenia. These cytopenias elevate the risk of severe infections, transfusion dependence, and prolonged hospital stays, contributing substantially to morbidity and non-relapse mortality. This review delineates the incidence, mechanisms, and risk factors for ICAHT, highlighting the complex interplay between disease burden, patient immune status, and CAR-T product features. Standardized grading systems, based on the depth and duration of neutropenia, have improved ICAHT classification and enabled more consistent risk stratification. Current prophylactic and therapeutic strategies ranging from growth factor administration to hematopoietic stem cell boosts for refractory cases are discussed, emphasizing tailored approaches to mitigate severe and prolonged hematotoxicity. These management strategies highlight the need for targeted interventions to prevent ICAHT without compromising CAR-T efficacy. As CAR-T therapy broadens to new indications, optimized ICAHT management could enhance patient outcomes, reduce healthcare utilization, and increase therapy accessibility.
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spelling doaj-art-e999e148aa344bfca978ef0abb5931ac2025-08-20T02:14:37ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-02-01999110.3324/haematol.2024.286027Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategiesOfrat Beyar-Katz0Kai Rejeski1Roni Shouval2Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion, HaifaAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA; Department of Medicine III – Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany; Bavarian Cancer Research Center (BZKF), partner site Munich, MunichAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for hematologic malignancies. However, it is frequently complicated by immune effector cell-associated hematotoxicity (ICAHT), a potentially life-threatening adverse event encompassing neutropenia, anemia, and thrombocytopenia. These cytopenias elevate the risk of severe infections, transfusion dependence, and prolonged hospital stays, contributing substantially to morbidity and non-relapse mortality. This review delineates the incidence, mechanisms, and risk factors for ICAHT, highlighting the complex interplay between disease burden, patient immune status, and CAR-T product features. Standardized grading systems, based on the depth and duration of neutropenia, have improved ICAHT classification and enabled more consistent risk stratification. Current prophylactic and therapeutic strategies ranging from growth factor administration to hematopoietic stem cell boosts for refractory cases are discussed, emphasizing tailored approaches to mitigate severe and prolonged hematotoxicity. These management strategies highlight the need for targeted interventions to prevent ICAHT without compromising CAR-T efficacy. As CAR-T therapy broadens to new indications, optimized ICAHT management could enhance patient outcomes, reduce healthcare utilization, and increase therapy accessibility. https://haematologica.org/article/view/11947
spellingShingle Ofrat Beyar-Katz
Kai Rejeski
Roni Shouval
Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies
Haematologica
title Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies
title_full Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies
title_fullStr Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies
title_full_unstemmed Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies
title_short Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies
title_sort immune effector cell associated hematotoxicity mechanisms clinical manifestations and management strategies
url https://haematologica.org/article/view/11947
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