Intensive treatments with stem cell autografts
Lymphoma cells are sensitive to chemotherapy. The higher the dose of chemotherapy, the more effect it will have on the cells. However, in practice, increasing the chemotherapy doses is limited by the increase of toxicity, especially for the blood cells. It is to allow very intensive treatments that therapeutical intensifications with stem cell autografts have been developed.
Stem cells are the cells that give birth to all the blood cells (red blood cells, white blood cells and platelets). They are found in the bone marrow (in all the bones of the pelvis, the sternum and the ribs in adults), but they are capable of circulating in the blood. They are then called peripheral stem cells. These cells carry a molecule that is detectable, called CD34. We then talk about CD34+ cells. Chemotherapy and growth factors (filgrastim, lenograstim) favour the circulation of these stem cells.
A therapeutic intensification with stem cell autografts is usually conducted as follows: stem cell sample, freezing of this sample, therapeutic intensification, then autograft.
Stem cell sample
The patient is injected with growth factors that ensure a good circulation of the stem cells. The number of stem cells circulating in the blood, CD34+, is monitored when the number of white blood cells increases. If the number of circulating stem cells is satisfactory, the sample is taken with a device that selects the part of the blood containing the stem cells. This cytapheresis lasts approximately 3 hours. It requires injecting a needle into a vein to sample the blood, and another to reinject the part that is not sampled. Between one and three cytaphereses are usually sufficient to gather the sample necessary for a therapeutic intensification.
In rare cases, there are not enough circulating stem cells to take a satisfactory sample. This makes it necessary to take a stem cell sample directly from the bone marrow. This sample requires general anaesthesia and the stem cells are sampled by punctures in the pelvic bone.
Stem cell freezing
The sample is then frozen after being tested. The frozen cells can be stored for several years.
The large doses administered in this stage make it possible to overcome the resistance of diseased cells, which is the aim of the treatment. This intensification lasts 6 to 7 days, and consists of:
- either a very high dose chemotherapy, usually the BEAM protocol (for BCNU, etoposide, aracytine and melphalan);
- or the association of a Total Body Irradiation (TBI) and a very high dose chemotherapy;
- or, more recently, the association of BEAM and Zevalin (administered one week before): Z-BEAM.
Stem cell autograft
One to three days after the end of the therapeutic intensification, the stem cells are unfrozen and transfused back into the patient. These cells will then settle in the bone marrow, and produce blood cells after 10 to 20 days. During this period of “aplasia”, during which the blood cell count is very low due to the high doses of chemotherapy and not yet reestablished by the injected stem cells, the patient is usually placed in an environment that protects them from infections. The entirety of this treatment requires a 3 to 4-week hospitalisation in a highly specialised service.