Lymphodepletion before CAR-T
A short course of chemotherapy (usually fludarabine and cyclophosphamide) given in the days before a CAR-T infusion to clear out the patient's own lymphocytes, making room and growth signals for the engineered cells to expand.
Lymphodepletion removes regulatory T cells and cytokine sinks, raising IL-7 and IL-15 levels so infused CAR-T cells proliferate; its intensity correlates with expansion, response and also toxicity. Fludarabine shortages led to bendamustine substitution with similar outcomes. It causes a week or two of cytopenias and infection risk and contributes to prolonged cytopenias after CAR-T. In vivo CAR-T approaches and some allogeneic products aim to work without lymphodepletion, which would remove a major barrier to outpatient and community delivery. Vein-to-vein time includes the wait for manufacturing before lymphodepletion can begin.
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