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Why is a bone marrow transplant done?
Bone marrow is the living tissue in the centre of our bones. Bone marrow contains blood stem cells, which constantly divide to provide a renewable supply of white cells, red cells and platelets. All of these different types of blood cell are crucial to human health. Without them, we become vulnerable to infections, anemia and bleeding which if not treated can be fatal. Bone marrow transplantation is performed when a patient's marrow is so diseased or damaged that it no longer functions properly. The procedure was first introduced in the 1970s and still offers the best chance to patients with blood cancers, as well as malignancies which require treatment with high doses of chemotherapy or radiotherapy. In addition bone marrow transplantation is sometimes used to treat certain inherited, immunodeficiency conditions.
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How is a bone marrow transplant done?
The basic principle of a bone marrow transplant is the implantation of healthy blood stem cells to the patient, in the hope that the transplanted cells will 'repair' the bone marrow and restore its normal function. The critical step in this procedure is 'engraftment', meaning that the transplanted cells thrive inside the patient and repopulate the bone marrow. If engraftment is successful, the transplanted cells will start to produce new healthy blood cells within 2-3 weeks.
In some cases the transplanted cells may be from the patient, this being known as an autologous transplant. In most cases however this is not appropriate due to this risk of putting diseased cells back into the patient. Therefore, in the majority of cases cells from a healthy donor are used. This is known as an allogeneic transplant. The key steps in an allogeneic bone marrow transplant for leukemia are as follows:
- A suitable source of donor cells is identified: this is usually from a sibling, alternatively a parent or child, or from an unrelated, volunteer donor.
- Donor cells are harvested from the bone marrow or peripheral blood.
- Patients undergo 'conditioning' such as chemotherapy: this aims to kill the malignant cells present in the bone marrow before the healthy donor cells are transferred. Sometimes complete ablation of the bone marrow is the goal (high intensity conditioning), but in older, less fit patients partial clearance may be attempted (reduced intensity conditioning).
- Donor cells are infused into the patient: this is done in a similar way to a blood transfusion i.e. through an intravenous line. The volume of cells and time taken to infuse can vary depending on the way the donor cells were collected.
- Patient is closely monitored following the transplant: the first sign of successful engraftment is usually an improved white blood cell count.
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What factors determine whether a bone marrow transplant will be successful?
- Donor and patient should be closely matched in terms of 'tissue type'. Tissue type is defined by molecules called HLA (human leukocyte antigens) on the surface of our cells. The lower the match between donor and patient HLA molecules, the lower the chance of engraftment. HLA types are genetically determined, hence close family members provide the closest match. Even siblings do not provide a 100% match, this is only seen with identical twins.
- Management of the patient during the engraftment phase is critical: At this stage bleeding and anemia are common and therefore blood and platelet transfusions are administered. In addition 'growth factors' may be given which encourage donor cell engraftment. In order to protect from infections, patients are given antibiotics and anti-fungal agents and are kept in protective isolation, in order to minimize their contact with infectious organisms. Visitors are required to wash their hands and 'gown up'.
- Bone marrow transplants can result in fatal complications, since the donor cells can recognize the patient tissues as 'foreign' and attack them. This is known as graft versus host disease (GvHD) and is one of the most common dangers of a bone marrow transplant. However, GvHD can often be controlled by immunosuppressive drugs, and leukemia patients who survive this phenomenon often have an improved outcome. This is because the donor cells, whilst attacking the patient’s cells have killed malignant cells in the process, this being known as the graft versus leukemia effect.