Treatment process: Planning and implementation of CAR T-cell therapy
Author: Julia Dobke, Editor: Maria Yiallouros, English Translation: Dr. med. Gesche Riabowol (geb. Tallen), Last modification: 2025/12/16 https://kinderkrebsinfo.de/doi/e217401
Table of contents
Each patient to undergo CAR T-cell therapy receives their individually designed treatment plan with the following treatment phases:
- First, T lymphocytes are removed from the patient by leukapheresis.
- Then, CAR T cells are produced individually for each patient in the laboratory. Depending on the lab, time of genetic engineering may vary.
- In the interim, many patients receive bridging chemotherapy.
- Before administering the CAR T cells, all patients receive chemo-therapy to reduce lymphocytes in the blood and bone marrow, also known as lymphodepletion. Lymphodepletion is usually carried out directly prior to CAR T-cell administration.
Leukapheresis (collection of white blood cells)
Leukapheresis (apheresis means “blood washing”) serves to separate white blood cells (leukocytes) from the other blood components. Leukocytes consist of three subgroups, each of which has different functions in the immune defence. A distinction is made between granulocytes, lymphocytes and monocytes. A certain number of T lymphocytes is required for the production of CAR T cells. These can be filtered out of the blood by leukapheresis.
Leukapheresis itself takes about three to four hours and is carried out via two venous approaches: the blood is taken via one and flows back into the vein via the other. A central venous catheter such as the Broviac catheter or Hickman catheter, which many patients have already received as part of conventional treatment, can also be used for this purpose.
The most common side effects of leukapheresis are fatigue, headaches as well as muscle cramps, which can usually be reduced by administering calcium. Normally, a single leukapheresis session is sufficient to filter out the T lymphocytes.
Bridging chemotherapy
The production of CAR T cells in the lab can take up a few weeks. Therefore, bridging chemotherapy is usually carried out until lymphocyte reduction measures (lymphodepletion) can be initiated (see below). The aim of bridging chemotherapy is to keep the patient's tumour burden under control prior to CAR T-cell administration. For patients with acute lymphoblastic leukaemia (ALL), this means that an increased production of lymphoblasts in the bone marrow is prevented. Frequently used medications include dexamethasone and vincristine.
Lymphodepletion
Lymphodepletion prior to administration of the CAR T cells serves to reduce the number of a patient’s leukaemia (or lymphoma) cells as well as other immune cells in order to make room for the CAR T cells. For lymphodepletion, the patient is usually admitted to the hospital.
Prior to lymphodepletion, it must be ensured that
- the patient does not have any infection,
- their kidney function is unimpaired,
- their heart function is unimpaired,
- the patient does not have any neurological impairment.
Two chemotherapeutic agents are usually given for lymphodepletion, such as fludarabine and cyclophosphamide. These are administered intravenously over a total of three to four days.
CAR T-cell reinfusion
The CAR T cells are administered as a short infusion via the patient’s central venous catheter. Beforehand, the patient receives certain medications to prevent allergic reactions and fever. In order to be able to detect side effects and reactions to the infusion as early as possible, the patient's vital signs are continuously monitored. Since acute adverse events usually do not occur until a few days after the CAR T-cell administration, patients should be monitored as inpatients for about 14 days.