Whether T cells are genetically engineered or not, before reinfusion, lymphodepletion of the recipient is required to eliminate regulatory T cells as well as unmodified, endogenous lymphocytes that compete with the transferred cells for homeostatic cytokines. Lymphodepletion may be achieved by myeloablative chemotherapy, to which total body irradiation may be added for greater effect. Transferred cells multiplied "in vivo" and persisted in peripheral blood in many people, sometimes representing levels of 75% of all CD8+ T cells at 6–12 months after infusion. , clinical trials for metastatic melanoma were ongoing at multiple sites. Clinical responses to adoptive transfer of T cells were observed in patients with metastatic melanoma resistant to multiple immunotherapies.