Different mechanisms can contribute to the failure of DLT to eradicate leukemia. Leukemia cells may persist in immunologically privileged sites, such as the central nervous system (CNS) and gonads or in extramedullary sites like the skin or the kidney, while still showing a continued remission in marrow. Malignant cells may escape immune detection and elimination if they have an altered expression of target antigens or costimulatory molecules required for efficient recognition. They may also directly down-regulate effector cells through secretion of inhibitory cytokines. Modulation of expression of FAS or FAS-ligand can also contribute to tumor escape from immune control.