Monocytes and macrophages in CAR T-cell-associated hematotoxicity: mechanisms linking inflammatory amplification to hematopoietic suppression and opportunities for clinical translation

Immune effector cell-associated hematotoxicity (ICAHT) is a clinically important complication of chimeric antigen receptor (CAR) T-cell therapy. It may present as early, prolonged, or late-onset neutropenia, anemia, and thrombocytopenia, and cannot be fully explained by lymphodepleting chemotherapy or treatment-related depletion of bone marrow reserve. A growing body of clinical and experimental evidence suggests that post-infusion hyperinflammation impairs hematopoietic recovery. Monocytes and macrophages may form a critical cellular link between T-cell activation, inflammatory amplification, and hematopoietic suppression. Monocytes and macrophages amplify CAR T-cell-associated cytokine release syndrome (CRS), but their contribution to persistent ICAHT is less clearly defined. Distinguishing acute inflammatory amplification from sustained disruption of marrow function is essential for interpreting the available evidence. This review examines myeloid-cell activation and functional reprogramming after CAR T-cell therapy, with particular emphasis on how myeloid inflammation may contribute to ICAHT by directly impairing hematopoietic stem and progenitor cells, disrupting the bone marrow microenvironment, and perturbing granulopoiesis and erythropoiesis. We also assess the translational potential of myeloid-associated biomarkers and inflammation-directed therapies and identify questions that require longitudinal sampling of peripheral blood and bone marrow, multi-omics analyses, and functional validation.