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Bone marrow is a spongy material that is found in the hollow centres of some bones. It is important as it contains special cells known as stem cells.
Stem cells create other specialised cells that carry out important functions. Stem cells in bone marrow produce three important types of blood cells:
Bone marrow transplantation
Bone marrow transplantation (also known as stem cell transplantation) involves harvesting healthy stem cells to replenish the bone marrow of a patient. The new stem cells take over the production of the blood cells.
In some circumstances, it may be possible to take your own bone marrow from another part of your body (this is known as autologous transplantation). The bone marrow is cleared of any diseased cells before being returned.
For more information see How is it performed?
Undergoing a stem cell transplant can be an intensive and challenging experience. The medicines used to prepare the body can cause unpleasant side effects and there is a risk of complications, such as your body rejecting the new stem cells, the new stem cells attacking your body (known as graft-versus-host disease) and infection.
Many people will take up to one year to recover fully from the procedure.
Other types of stem cell transplantation
In the past, doctors were only able to get stem cells from bone marrow. However, it is now possible to get them from other sources.
Peripheral blood stem cell donation
A special medicine can be injected into the donor's blood, which causes the stem cells to filter out of their bone marrow and into the bloodstream. Some of the blood can then be donated to the person who needs it. This is known as a peripheral blood stem cell (PBSC) donation. The advantage is that the donor does not need to take a general anaesthetic (where they are put to sleep).
Cord blood donation
Stem cells can be collected from the umbilical cord of a new born baby and stored for years in a laboratory until needed. This is known as a cord blood donation. It is important to note that stem cells are not collected from the baby, but from the blood of the cord and placenta (which are normally discarded). These cord blood stem cells are important because they do not need to be as closely matched as bone marrow or peripheral blood stem cells to ensure a successful outcome.
In October 2009, the NHS Cord Blood Bank opened its state-of-the-art storage facility at Filton, Bristol. The NHS Cord Blood Bank is the fourth largest in the world, with 14,500 donations available for therapeutic use. Deposits will be increased to 20,000 donations by 2013.^^ Back to top
Stem cell transplantations are often required to treat conditions that have damaged the bone marrow which, as a result, can no longer produce normal blood cells. Any disruption to the production of blood cells can be very serious, particularly if:
Some of the conditions that can affect blood and bone marrow are described below.
Leukaemia is cancer of the white blood cells. The cancer causes the white blood cells to replicate in an uncontrollable manner and they do not develop any infection-fighting properties.
The cancerous cells can quickly spread through the bloodstream, resulting in a lack of room for red blood cells and platelets.
This leads to symptoms of anaemia, increases the risk of serious infection, and means that you will bruise and bleed more easily.
Non-Hodgkin's lymphoma is another type of cancer of the white blood cells. However, rather than spreading through the bloodstream, it spreads through the lymphatic system. The lymphatic system is a series of connected glands (nodes) that are spread throughout your body. It is an important part of your immune system, the body's natural defence against infection.
Inherited (genetic) blood disorders
There are a number of genetic blood disorders where alterations (mutations) in your genes mean that blood cells do not develop normally. These include sickle cell anaemia and thalassaemia, both of which interfere with the production of red blood cells.^^ Back to top
Stem cell transplants are normally only recommended if:
The importance of tissue type
All human tissue carries a special genetic 'marker' or code, known as a human leukocyte antigen (HLA). Ideally, you should receive your transplant from somebody with an identical or very similar HLA tissue type.
This is because if the transplanted tissue has a different HLA type, your immune system might regard it as a foreign object and reject the transplant.
Alternatively, the cells from the transplanted tissue may regard the rest of your body as a foreign object and begin attacking it, leading to graft versus host disease.
Your HLA is inherited from your parents. If you have a brother or a sister who is willing to be a donor, they will need to be tested to see if their HLA type is the same. There is a one-in-four chance that each sibling will be an exact match.
National Bone Marrow Registry
If none of your siblings are suitable donors or if you are an only child, a search of the British Bone Marrow Registry will be conducted. The British Bone Marrow Registry contains a list of all the people willing to donate stem cells, along with their HLA type.
You may have to wait several years before a suitable donor can be found. However, in some rare cases, waiting without treatment may be considered too dangerous, so a partially matched donor may be used instead. This will increase the risks of complications, but your treatment team may recommend it if they feel that the benefits outweigh the risks.^^ Back to top
There are five stages in the transplant process:
A thorough physical examination is recommended before having a stem cell transplant. This is because your general health before the transplant will play a big part in how well you recover after the procedure.
As part of the examination, scans may be used to check the condition of internal organs, such as your liver, heart and lungs. Some of the medicines that are used in the conditioning and recovery process can occasionally cause problems with the organs, so it is important to know how well they are functioning before the transplant can begin.
After the transplant , you will be more prone to infection, so it is therefore vital to ensure that you do not have any current underlying infections.
If you have a cancer-related condition, you may need to have a biopsy. A biopsy is a surgical procedure where a small sample of cancerous cells are removed and checked in a laboratory. A biopsy can show if your cancer is in remission and whether or not there is not a high risk of it returning after your transplant.
Obtaining the stem cells
Once the physical examination has taken place, it will then be necessary to harvest the stem cells.
The usual method is to take blood from the body, separate the stem cells from the other cells in the blood and return the blood.
The other way is to extract the marrow itself, removing stem cells from the hip bone using a special needle and syringe.
Your own stem cells can be used if they are suitable (this is called autologous transplantation). They can be harvested using either method above. Your stem cells will need to be treated with high doses of radiation or chemotherapy to ensure there are no cancerous cells left.
If it is performed as a bone marrow transplant, about a litre of bone marrow will be removed by needle, normally from your hip bone when you are under general anaesthetic (put to sleep). The procedure is low risk, but the area where the needle was used may be painful afterwards.
You may need to have this procedure several times before enough bone marrow is harvested.
If your stem cells are not suitable, cells will be harvested from a healthy donor. This is known as allogenic transplantation.
At present, there are more than 400,000 potential donors on the UK bone marrow register but more are needed from many ethnic groups because tissue types have to be a good match. There is a particular shortage of donors from African, African-Caribbean, Asian, Jewish, eastern European and Mediterranean communities. The identity and location of both donor and patient will remain confidential.
The process of harvesting cells from a healthy donor is similar to an autologous transplantation. For four days before, the donor will be given a drug that stimulates production of stem cells in their blood. On the fifth day, they will have a blood test to check that they have enough circulating stem cells. They will then be connected to a cell-separator machine, without the need for a general anaesthetic, which means the harvesting can be carried out as an outpatient procedure.
Blood is removed through a vein in one arm, passed through a filtering machine to separate the stem cells from other cells in the blood, and returned to the body through a vein in the other arm. The donor may be asked back on the sixth day for another donation, if the dose of cells obtained is not sufficient. This procedure usually requires about two sessions of two to three hours on successive days.
Removal of bone marrow from the hip bones is done using a needle and syringe under a general anaesthetic in hospital. Although this is not a surgical operation, there will be marks on the skin made by the needle. As there may be some discomfort where the needle has been inserted, the donor will need to stay in hospital for up to 48 hours and have a period of recovery at home of up to five days.
Preparing your body
As you will need to receive many medicines as part of your conditioning, a tube will be inserted into a large vein near your heart. This is known as a central line, which will avoid the need to have many painful injections.
The conditioning process involves using high doses of chemotherapy and possibly radiation. This is done for three reasons:
The conditioning process normally takes 4-7 days. You will probably need to stay in hospital throughout the procedure. Side effects from the chemotherapy are common, including:
The side effects can last several weeks after the conditioning has finished, although mouth ulcers and skin rashes should stop once the transplanted tissue begins producing new blood cells. Hair usually grows back within 3-6 months.
Less common side effects of the conditioning process are lung damage and a condition known as veno-occlusive disease. Veno-occlusive disease causes the blood vessels in your liver to swell, which will stop your liver removing waste products from your body. This can cause abdominal pain, jaundice (yellowing of the skin) and weight gain (see Risks for more information).
Veno-occlusive disease can be treated using medicines that help to prevent blood clots and blood transfusions, and by reducing the amount of salt in your diet. Lung damage or lung infection can be treated with oxygen, and steroids (strong medicine) may also be given.
The transplant can normally be performed 1-2 days after your conditioning has finished. The donated stem cells are passed into your body through the central line. This normally takes about an hour to complete. You will be awake during the transplant procedure, which is not painful.
After the transplant, you will be weak and may have lack of appetite, vomiting and diarrhoea. To prevent malnutrition, you will need nutritional support with high-protein fluids taken by mouth or through a tube running through your nose to your stomach or through a vein.
The first stage of recovery is to wait for the stem cells to make their way to your bone marrow and begin making new blood cells, which is known as engraftment. Engraftment normally happens 15-30 days after the transfusion takes place.
While waiting for engraftment, you will need to receive regular blood transfusions because you will have a low number of red blood cells.
You will also be at high risk of infection as you will also have a low number of white blood cells. Therefore, you will need to stay in hospital in a germ-clean (sterile) environment. You may be allowed visitors, but it is likely that they will have to wear surgical masks, gowns, and gloves to prevent infection. Antibiotics may also be prescribed to prevent infection.
Once engraftment has taken place, your body will begin producing blood cells. However, you will still be very weak because of the effects of the chemotherapy.
You will also still be at high risk of developing an infection. This is because it can take several years for your immune system to return to its full strength. Also, you may be given medicines that stop your immune system from working (immunosuppressants) to prevent graft versus host disease. As a result of this, you may not be well enough to leave the hospital until three months after your transfusion.^^ Back to top
Stem cell transplantation is a complicated procedure with significant risks of serious complications.
Generally, risks are reduced if:
As the risk of complications resulting from transplantation is significant, it is important that you are fully aware of the risks and possible benefits of the treatment before it begins. You may wish to discuss the risks and benefits with your treatment staff and with your family beforehand.
The major problem with stem cell transplantation is the ability of the patient to withstand the high doses of chemotherapy and radiotherapy usually given before the transplant.
Many conditions for which a donor stem cell transplant is necessary affect older patients. An autologous transplant is generally considered less dangerous than an allogeneic transplant, so the upper age limit at most centres is about 55 years for the allogeneic transplant and between 60 and 70 years for an autologous transplant.
The main risks arising from a stem cell transplant are discussed below.
Graft verses host disease (GVHD)
Graft verses host disease (GVHD) is a common complication of stem cell transplantation. It happens because the cells in the transplanted tissue (graft cells)do not recognise the patient's (host) cells and try to attack them.
There are two types of GVHD:
The symptoms of acute GVHD include:
Chronic GVHD usually develops three months after the transplant. The symptoms can persist or come and go for many years. The severity of the symptoms can range from mild to life threatening.
Symptoms of chronic GVHD include:
In the most serious cases of GVHD, the function of the liver or the lungs can be affected, which can be fatal.
GVHD can be treated using immunosuppressants, usually along with corticosteroids. Immunosupressants stop the transplanted tissue releasing antibodies that would attack the rest of your body. However, they will also affect the rest of your immune system, putting you at a higher risk of infection.
Corticosteroids are a type of medicine that contain powerful hormones called steroids. They can cause side effects, including:
If you have a transplant, you will be at an increased risk of developing an infection. This is because the conditioning you received before the transplant will have weakened your immune system. This risk may be increased if you need to take immunosuppressants.
It is very important to try to prevent an infection occurring because an infection can rapidly develop into a more serious condition, such as a lung infection (pneumonia).^^ Back to top
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