fludarabine + cyclophosphamide + CAR-T cells

This regimen combines two chemotherapeutic agents, fludarabine and cyclophosphamide, with chimeric antigen receptor T-cell (CAR-T) therapy. Fludarabine and cyclophosphamide are used as lymphodepleting agents to reduce the patient’s existing immune cells before infusion of genetically engineered autologous T-cells (CAR-T cells). The purpose of this preconditioning is to enhance the expansion and persistence of infused CAR-T cells. - **Fludarabine** is a purine analog that inhibits DNA synthesis by interfering with DNA polymerase and ribonucleotide reductase activity. - **Cyclophosphamide** is an alkylating agent that crosslinks DNA strands, leading to cell death in rapidly dividing lymphocytes. - **CAR-T cell therapy** involves collecting a patient’s own T-cells, genetically modifying them ex vivo to express a chimeric antigen receptor targeting specific tumor antigens (such as CD19), expanding these modified T-cells in the laboratory, then infusing them back into the patient[1][3][4][5]. The engineered receptors enable T-cells to recognize and kill cancer cells through direct cytotoxicity (perforin/granzyme pathway), induction of apoptosis via Fas/FasL interactions, secretion of inflammatory cytokines (e.g., IL-2, IFN-gamma), and other mechanisms[1][4]. This combination regimen is primarily used for relapsed or refractory B-cell malignancies such as diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), follicular lymphoma (FL), acute lymphoblastic leukemia (ALL), among others[8].

Other names

lymphodepleting chemotherapy plus CAR-T cell therapyfludarabine/cyclophosphamide preconditioning plus CAR-T cells