Immune effector cell-associated hematotoxicity: Mechanisms, clinical manifestations, and management strategies Review
| Authors: | Beyar-Katz, O.; Rejeski, K.; Shouval, R. |
| Review Title: | Immune effector cell-associated hematotoxicity: Mechanisms, clinical manifestations, and management strategies |
| Abstract: | 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, a patient’s immune status, and features of the CAR T-cell products. Standardized grading systems, based on the depth and duration of neutropenia, have improved the classification of ICAHT 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 the efficacy of the CAR T cells. As CAR T-cell therapy broadens to new indications, optimized ICAHT management could enhance patients’ outcomes, reduce healthcare utilization, and increase therapy accessibility. ©2025 Ferrata Storti Foundation. |
| Keywords: | neutropenia; review; anemia; blood toxicity; thrombocytopenia; risk factor; health care utilization; immunology; hematologic malignancy; hematologic neoplasms; diagnosis; chimeric antigen receptor; effector cell; hematopoietic stem cell; disease management; drug therapy; cytopenia; adverse drug reaction; therapy; adoptive immunotherapy; immunotherapy, adoptive; hematologic disease; pharmacology; etiology; adverse event; procedures; immune status; humans; human; chimeric antigen receptor t-cell immunotherapy; chimeric antigen receptor t-cell; receptors, chimeric antigen |
| Journal Title: | Haematologica |
| Volume: | 110 |
| Issue: | 6 |
| ISSN: | 0390-6078 |
| Publisher: | Ferrata Storti Foundation |
| Date Published: | 2025-06-01 |
| Start Page: | 1254 |
| End Page: | 1268 |
| Language: | English |
| DOI: | 10.3324/haematol.2024.286027 |
| PUBMED: | 39973361 |
| PROVIDER: | scopus |
| PMCID: | PMC12130777 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
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