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 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.