Prolonged Cytopenia with CAR-T Cell Therapy and Management Recommendations

Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment of lymphoid malignancies. Prolonged cytopenias, though poorly understood, have emerged as important considerations in the treatment process. In this review, we classified cytopenias into early (< 30 days post CAR T infusion), and late-occurring (after day 30 post infusion). We identified previous chemotherapy and lymphodepletion chemotherapy as the major risk factors contributing to early cytopenia. Product characteristics, such as costimulatory domains, and side effects of therapy such as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) were identified as contributing factors to prolonged cytopenias occurring more than 30 days post CAR-T infusion. We recommend close monitoring with frequent checks, enhanced care with granulocyte colony stimulating factor (GCSF) support for grade 3-4 neutropenia, blood transfusion for severe anemia (Hb < 7g/dL), platelets for severe thrombocytopenia (< 10,000/µL) and thrombopoietin (TPO) mimetics such as eltrombopag or romiplostim for prolonged severe thrombocytopenia in patients at high-risk of hemorrhagic complications.