What is a bone marrow transplant?
A bone marrow transplant, more commonly known as a stem cell transplant, replaces damaged bone marrow with healthy bone marrow stem cells.
Bone marrow is a spongy tissue found in the hollow centres of some bones. It contains specialist stem cells which produce the body's blood cells.
Stem cells in bone marrow produce three important types of blood cells:
- red blood cells – which carry oxygen around the body
- white blood cells – which help fight infection
- platelets – which help stop bleeding
What is a bone marrow transplant?
A bone marrow transplant involves taking healthy stem cells from the bone marrow of one person and transferring them to the bone marrow of another person.
Bone marrow transplants are often needed to treat conditions that damage bone marrow meaning that it is no longer able to produce normal blood cells. The new stem cells take over blood cell production.
Bone marrow transplant is used to treat:
- severe aplastic anaemia (bone marrow failure)
- leukaemia – cancer of the white blood cells
- – cancer of the lymphatic system
- certain genetic blood and immune system disorders – such as , and some severe immune system diseases
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.In some cases, it may be possible to take your own bone marrow from another part of your body (autologous transplantation). The bone marrow is cleared of any damaged or diseased cells before it is returned.
The transplant procedure
A bone marrow transplant involves five stages. These are:
- a physical examination to assess your general level of health
- obtaining the stem cells to be used in the transplant (known as harvesting)
- preparing your body for the transplant (known as conditioning)
- transplanting the stem cells
- the recovery period during which you will be monitored for any complications or side effects
Having a bone marrow transplant can be an intensive and challenging experience. Many people take up to a year to fully recover from the procedure.
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.Who can have a bone marrow transplant?
Bone marrow transplants are usually only recommended if:
- the recipient is in relatively good health despite their associated condition (which is why they are often carried out when cancer is in remission)
- stem cells are available from a brother or sister or, less commonly, another family member, or an unrelated donor with the same or similar tissue type (this reduces the chances of the bone marrow being rejected)
- the associated condition is not responding to other forms of treatment and it is felt that the condition would respond to a transplant and could get worse without one
- it is felt that the benefits of a transplant outweigh the risks
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.Risks
Bone marrow transplants are complicated procedures with significant risks.
In some cases the transplanted cells (graft cells) recognise the recipient's cells as 'foreign' and try to attack them. This is known as graft versus host disease (GvHD).
The risk of infection is also increased because the immune system is weakened as you are conditioned (prepared) for the transplant.
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.Bone marrow transplant risks
Bone marrow transplants are complex procedures that carry significant risks of serious complications.
Generally risks are reduced if:
- you are young – studies have shown the younger you are, the more likely the treatment is to succeed
- you receive a donation from a brother or sister
- you have no other serious health conditions, apart from the condition that you are being treated for
As there is a significant risk of complications occurring after a bone marrow transplant, it is important you are fully aware of both the risks and possible benefits before treatment begins. You may wish to discuss these with your treatment team and your family.
The major problem with stem cell transplants is the recipient's ability to withstand high doses of
(and sometimes ) often needed before the transplant.Many conditions for which a bone marrow transplant is required affect older people. An autologous transplant (where the patient's own stem cells are used) is generally considered less risky than an allogeneic transplant (where a donor's stem cells are used).
Therefore, the upper age limit at most centres is around 55 years of age for an allogeneic transplant and 60-70 years for an autologous transplant.
The main risks associated with a bone marrow transplant are discussed below.
Graft versus host disease
In some cases, the transplanted cells (graft cells) recognise the recipient's cells as 'foreign' and try to attack them. This is known as graft versus host disease (GvHD) and it often occurs following stem cell transplantation.
There are two types of GvHD, they are:
- acute GvHD – which usually happens during the first three months of the transplant
- chronic GvHD – which develops from acute GVHD and can cause symptoms for many years
The symptoms of acute GvHD include:
- red spots on the hands, feet and face which then spread across the body into a rash
- the rash may then develop into blisters
- a fever (high temperature) of 38C (100.4F) or above
- bloody or watery
- stomach cramps
- – yellowing of the skin and whites of the eyes (although this is a rare symptom of acute GvHD)
Chronic GvHD can develop anywhere between three months and two years after the transplant. The symptoms can persist or they may come and go for many years. They can range in severity from mild to life-threatening.
Symptoms of chronic GvHD include:
- an itchy, dry rash that can spread over the entire body
- dry and sensitive mouth
- hardening of the skin
In particularly serious cases of GvHD, lung or liver function can be affected which can be very serious.
GvHD can be treated using immunosuppressants, usually in conjunction with
(see below).Immunosuppressants stop the transplanted tissue releasing antibodies that would otherwise attack the rest of your body. However, they will also affect the rest of your immune system, placing you at a higher risk of infection.
Corticosteroids are a type of medication containing powerful hormones. They can help suppress (control) the exaggerated immune response that leads to GvHD. However, corticosteroids can cause a number of side effects including:
- high blood sugar levels
- increased appetite
- mood changes
- vomiting
- diarrhoea
- itchiness
- hypertension (high blood pressure)
Infection
After having a bone marrow transplant, your risk of developing an infection will be increased. This is because the conditioning you receive before the transplant will weaken your immune system. The risk of infection may be further increased if you need to take immunosuppressants.
It is very important to prevent infections developing. If you get an infection it could quickly develop into a more serious condition such as a lung infection (
).How is a bone marrow transplant performed?
Having a bone marrow transplant is a complicated five stage process.
The five stages are:
- a physical examination of your body to assess your general level of health
- obtaining the stem cells that will be used in the transplant (known as harvesting)
- preparing your body for the transplant (known as conditioning)
- transplanting the stem cells
- the recovery period, during which you will be monitored for any complications or side effects
The five stages are described in more detail below.
Physical examination
You will have a thorough physical examination before having a stem cell transplant. Your overall level of health before the transplant will play a big part in how well you recover after the procedure.
As part of the examination, you may have some scans to check the condition of internal organs, such as your liver, heart and lungs.
Some medicines used in the conditioning and recovery process can occasionally cause problems with your organs, so it is important to know how well they are functioning beforehand.
After the transplant, your risk of developing an infection will be increased, so it is vital to ensure you do not have any current underlying infections.
If you have a cancer-related condition, you may need to have a biopsy. This involves removing a small sample of cancerous cells so they can be checked in a laboratory.
The results of a biopsy can show whether your cancer is in remission (under control) and whether there is a high risk of it returning after your transplant.
Obtaining stem cells
When you've had a physical examination, the stem cells will need to be harvested.
The usual method involves removing blood from the body, separating the stem cells from the other cells in the blood and then returning the blood to the body.
Alternatively, the bone marrow itself can be collected by removing stem cells from the hip bone using a special needle and syringe. This may be recommended for certain conditions that require a transplant, or if the donor is a child.
Autologous transplantation
If they are suitable, it may be possible to use your own stem cells. This is known as an autologous transplantation. They can be harvested using either method described above.
Your stem cells may need to be treated with
or to ensure that there are no cancerous cells left.If your bone marrow is being extracted, a needle will be used to remove about a litre of bone marrow. It will usually be removed from your hip bone while you are under general anaesthetic. The procedure is low risk but the area where the needle is inserted may be painful afterwards.
The procedure may need to be carried out several times before enough bone marrow is harvested.
Allogeneic transplantation
If your own stem cells are not suitable, stem cells will be harvested from a healthy donor. This is known as allogeneic transplantation.
The more people who register for bone-marrow-transplant, the more chance there is of finding a matching tissue type for someone who needs a transplant. When a suitable donor is found, their identity and location and those of the patient remain confidential. However over time and if both sides want to this can be arranged.
The process of harvesting cells from a healthy donor is similar to the one used for an autologous transplant.
For four days before the transplant, the donor will be given medication to stimulate the production of stem cells in their blood. On the fifth day, they will have a blood test to check they have enough circulating stem cells.
They will then be connected to a cell-separator machine. A general anaesthetic is not needed, which means the harvesting can be done as an outpatient procedure.
Blood is removed through a vein in one arm and passed through a filtering machine to separate the stem cells from other blood cells. It is then returned to the body through a vein in the other arm.
If the number of cells obtained is insufficient, the donor may be asked to return on the sixth day to make another donation. The procedure usually requires about two sessions lasting 2-3 hours on successive days.
Removal of bone marrow from the hip bone is carried out in hospital, under general anaesthetic, using a needle and syringe.
Although it is not a surgical operation, some marks from the needle will be left on the skin. There may also be some discomfort where the needle has been inserted.
As a result, the donor will need to stay in hospital for up to 48 hours and have a period of recovery at home lasting up to five days.
Preparing your body
As part of your conditioning, you will need to be given a range of medicines, so a tube will be inserted into a large vein near your heart. This is known as a central line and will avoid the need for you to have many painful injections.
The conditioning process involves using high doses of chemotherapy and possibly radiation. It is done for three reasons:
- to destroy the existing bone marrow and make room for the transplanted tissue
- to destroy any existing cancer cells
- to stop your immune system working in order to reduce the chance of the transplant being rejected
The conditioning process usually takes four to seven days. You will probably need to stay in hospital throughout the procedure. Side effects from chemotherapy are common and include:
- nausea (feeling sick)
- vomiting
- loss of appetite
- tiredness
- skin rashes
The side effects can last for several weeks after the conditioning has finished, although mouth ulcers and skin rashes should stop once the transplanted tissue begins to produce new blood cells. Hair usually grows back within three to six months.
Two less common side effects of the conditioning process are lung damage and a condition called veno-occlusive disease.
Veno-occlusive disease causes the blood vessels in your liver to swell, stopping it from removing waste products from your body. This can cause abdominal pain,
(yellowing of the skin) and weight gain.Veno-occlusive disease can be treated with medicines to help prevent
, as well as using and reducing the amount of salt in your diet.Lung damage or a lung infection can be treated with oxygen, antibiotics and sometimes other treatments. Steroids (strong medication) may also be given to dampen potentially dangerous immune reactions.
Read more about the risks of bone marrow transplants.
The transplant
It is usually possible to carry out the transplant one to two days after conditioning has finished.
The donated stem cells will be passed into your body through the central line. The process can take from half an hour to several hours to complete, depending on the type of blood cells being used.
The transplant is not painful and you will be awake throughout the procedure.
Recovery
You may feel weak after the transplant, and you may experience vomiting,
and have a loss of appetite.To prevent
(a lack of essential nutrients), you will need to have nutritional support, with high-protein fluids taken by mouth or through a tube running through your nose to your stomach.The first stage of the recovery process involves waiting for the stem cells to reach your bone marrow and start producing new blood cells. This is known as engraftment and it usually occurs 15-30 days after the transplant takes place.
During this period, you will need to have regular blood transfusions because you will have a low number of red blood cells.
You will also be at increased risk of developing an infection because you will have a low number of white blood cells. This means that you will need to stay in hospital in a germ-free environment.
You may be allowed visitors, but it is likely they will have to wear surgical gowns and hats to prevent infection.
may also be used to either prevent or treat infections.Once engraftment has occurred, your bone marrow will begin producing blood cells. However, you will still be very weak due to the effects of the chemotherapy.
You will also still have a high risk of developing an infection because it can take one to two years for your immune system to return to its full strength.
You may also be given medicines that stop your immune system from working (immunosuppressants) to prevent graft versus host disease (GvHD).
Many people are well enough to be discharged from hospital one to three months after having a bone marrow transplant. However, if you develop complications, such as an infection, you may not be able to leave hospital until more than three months after the transplant.
Complications of bone marrow transplants
Due to the high risk of complications, bone marrow transplants are only recommended in certain situations where other treatments have failed.
Bone marrow transplants are usually only recommended if:
- the recipient of the transplant is in relatively good health despite their associated condition – which is why they are often carried out when is in remission
- stem cells are available from a brother or sister or, less commonly, another family member, or an unrelated donor, with the same or similar tissue type, which reduces the chances of bone marrow being rejected
- the associated condition is not responding to other forms of treatment, or it is felt that there is a high risk of the condition returning without a transplant
- it is felt that the benefits of a transplant outweigh the risks
Tissue type
All human tissue carries a special genetic marker or code which is known as a human leukocyte antigen (HLA).
For a transplant to be successful, the transplanted tissue should ideally come from someone with an identical or very similar HLA tissue type.
If the transplanted tissue has a different HLA type, your immune system might treat it as a foreign object and reject it.
Alternatively, the cells from the transplanted tissue may regard the rest of your body as a foreign object and start attacking it. This is known as graft versus host disease (GvHD).
Your tissue type is inherited from both of your parents. If you have a brother or sister who is willing to be a donor, they will need to be tested to see if their HLA type is the same as yours. There is a one in four chance of each full sibling – that is, those who share both of the same parents – being an exact match.
Bone marrow registry in the UK
If you are an only child, or if your siblings are not suitable donors, a search of the NHS Blood and Transplant registry will be carried out. It holds a database of all the people willing to donate stem cells and their HLA type.
It may take several years before a suitable donor can be found. However, in some cases waiting without treatment may be considered too dangerous or it may not be possible to find a full match. In such cases, stem cells from 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.
When is a bone marrow transplant needed?
Bone marrow transplants are often needed when a person's own bone marrow has been damaged and can no longer produce normal blood cells.
Any disruption to the production of blood cells can be very serious, particularly if:
- you do not have enough red blood cells – your body will be starved of oxygen, you will feel tired and faint and your organs may be damaged
- you do not have enough white blood cells – you will have a much higher risk of developing a serious infection
- you do not have enough platelets – you will bleed and bruise more easily
Some of the conditions that can affect blood and bone marrow are described below.
Bone marrow failure
The continuous process of producing blood cells and platelets to replace old cells is an essential part of healthy life. In adults, this reproduction process only occurs within bone marrow.
Therefore, a bone marrow transplant may be needed in cases where a person’s bone marrow fails (severe aplastic anaemia). This may be due to an inherited condition, such as a rare type of anaemia, or as the result of an acquired condition, such as
, Epstein-Barr virus (the virus that causes ) or [parvovirus B19.Leukaemia
Leukaemia is cancer of the white blood cells. The white blood cells replicate in an uncontrollable manner and do not develop any infection-fighting properties.
The cancerous cells can quickly spread through your bloodstream, resulting in a lack of room for red blood cells and platelets.
This can lead to the symptoms of
and increases your risk of serious infection. You will also bleed and bruise more easily.There are a number of different types of leukaemia where a bone marrow transplant may be needed. These are:
Non-Hodgkin's lymphoma
Non-Hodgkin's lymphoma is also a cancer of the white blood cells. However, unlike leukaemia it spreads through the lymphatic system rather than the bloodstream.
The lymphatic system is a series of connected glands (nodes) that are located around your body. It is an important part of the immune system which is your body's natural defence against infection and illness.
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.Genetic blood and immune system disorders
There are number of blood disorders where mutations (alterations) in your genes result in the blood cells not developing normally. These include
and . Both conditions interfere with the production of red blood cells.Immune system disorders can include a wide range of immunodeficiencies and some other genetic conditions.