Lymphodepleting

Lymphodepleting refers to the purposeful reduction or depletion of lymphocytes—primarily T cells, B cells, and natural killer cells—from the blood and bone marrow. This state is usually induced as part of a medical treatment rather than occurring spontaneously. Lymphodepletion is typically achieved through conditioning regimens that combine chemotherapy, radiation, or targeted biologic agents and is followed by immune-based therapies in some cases.

Common methods include chemotherapeutic regimens such as fludarabine and cyclophosphamide, total body irradiation, and monoclonal antibodies that deplete lymphocytes (for example alemtuzumab or anti-thymocyte globulin). These approaches may be used before procedures like hematopoietic stem cell transplantation or before adoptive cell therapies, including chimeric antigen receptor (CAR) T-cell therapy, to reduce host immune rejection, create space in the immune system, and promote the activity and persistence of infused cells.

The intended effects of lymphodepletion include improved engraftment, enhanced proliferation and function of transferred immune cells, and a more favorable cytokine environment. However, lymphodepletion carries risks such as increased susceptibility to infections, cytopenias, and delayed immune reconstitution. Patients require careful monitoring, prophylactic measures against infections, and management of treatment-related toxicities.

Lymphodepletion differs from lymphopenia in that the former describes a controlled, treatment-induced state, while the latter is a laboratory finding of low lymphocyte counts. The term “lymphodepleting” is used to describe regimens or agents designed to cause this depletion.