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Bone marrow transplant

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Bone marrow transplant



Introduction 

A bone marrow transplant, also known as a haemopoietic 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  



 

Why are bone marrow transplants needed?

Bone marrow transplants are often needed to treat conditions that damage bone marrow. If bone marrow is damaged, it is no longer able to produce normal blood cells. The new stem cells take over blood cell production.

Conditions that bone marrow transplants are used to treat include:



severe aplastic anaemia (bone marrow failure)



leukaemia – cancer of the white blood cells



non-Hodgkin lymphoma – cancer of the lymphatic system



certain genetic blood and immune system disorders – such as sickle cell anaemia, thalassaemia and some severe immune system conditions



 

What does a bone marrow transplant involve?

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.

In some cases, it may be possible to take the bone marrow from your own body. This is known as an autologous transplantation. Before it is returned, the bone marrow is cleared of any damaged or diseased cells.

A bone marrow transplant has five stages. These are:



physical examination – to assess your general level of health



harvesting – the process of obtaining the stem cells to be used in the transplant



conditioning – preparing your body for the transplant



transplanting the stem cells



recovery period –during which you'll 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.

 

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're often carried out when cancer is in remission)



stem cells are available from a brother/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 isn't responding to other forms of treatment and it's believed that it would respond to a transplant and could get worse without one



the benefits of a transplant are believed to outweigh the risks



 

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 your immune system is weakened when you're conditioned (prepared) for the transplant.  

 

Bone marrow transplant: Sarah's story

Sarah had leukemia and needed a bone marrow transplant. In this video she talks about her experiences.


Media last reviewed: 14/11/2013

Next review due: 14/11/2015

 


Other methods of stem cell donation

It's now possible to harvest stem cells from sources other than bone marrow.

Peripheral blood stem cell donation involves injecting a medicine into the donor's blood that causes the stem cells to move out of the bone marrow and into the bloodstream where they can be harvested (collected).

The advantage of this type of stem cell donation is that the donor doesn't need a general anaesthetic.

Stem cells can also be collected from the placenta and umbilical cord of a newborn baby and stored in a laboratory until they're needed.

Cord blood stem cells are very useful because they don't need to be as closely matched as bone marrow or peripheral blood stem cells for a successful outcome.

 

Why bone marrow transplants are necessary 

Bone marrow transplants are often needed when a person's own bone marrow has been damaged and can no longer produce normal blood cells.

Disruption to the production of blood cells can be very serious, particularly if you:



don't have enough red blood cells – your body will be starved of oxygen, you'll feel tired and faint and your organs could be damaged



don't have enough white blood cells – your risk of developing a serious infection will be significantly increased  



don't have enough platelets – you'll bleed and bruise more easily



Some of the conditions that can affect blood and bone marrow are described below.

 

Bone marrow failure

The continuous production of blood cells and platelets to replace old cells is essential for a healthy life.

In adults, this reproduction process only occurs within bone marrow. Therefore, a bone marrow transplant may be needed if your bone marrow fails (known as severe aplastic anaemia).

This may happen as a consequence of an inherited condition – a rare type of anaemia, for example. It could also be the result of an acquired condition, including rare complications of certain infections, such as hepatitis B, Epstein-Barr virus (which causes glandular fever) or parvovirus B19.

 

Leukaemia

Leukaemia is cancer of the white blood cells. The white blood cells replicate in an uncontrollable manner and don't develop any infection-fighting properties.

The cancerous cells can quickly spread through your bloodstream, leading to a lack of room for red blood cells and platelets.

This can lead to the symptoms of anaemia and increases your risk of serious infection. You'll also bleed and bruise more easily.

There are numerous types of leukaemia where a bone marrow transplant may be needed. These are:



acute lymphoblastic leukaemia



acute myeloid leukaemia



chronic lymphocytic leukaemia



chronic myeloid leukaemia



 

Non-Hodgkin lymphoma

Non-Hodgkin lymphoma is another 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's an important part of the immune system, which is your body's natural defence against infection and illness.

 

Genetic blood and immune system disorders

There are number of blood disorders where mutations (alterations) in your genes cause the blood cells to develop abnormally.

These include sickle cell anaemia and thalassaemia. 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.

 

Who can have a bone marrow transplant 

Bone marrow transplants are only recommended in certain situations, when other treatments have failed.

This is because there's a high risk of complications.

Bone marrow transplants are usually only recommended if:



the recipient is in relatively good health despite their associated condition (which is why they're often carried out when cancer is in remission)



stem cells are available from a brother/sister, or, less commonly, from another family member/unrelated donor with the same or similar tissue type (this lowers the chances of the bone marrow being rejected)



the associated condition isn't responding to other forms of treatment, and it's believed it would respond to a transplant and could get worse without one



the benefits of a transplant are believed to outweigh the risks



 

Tissue type

All human tissue carries a special genetic marker or code, 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 parents. If you have a brother or sister who's willing to be a donor, they'll need to be tested to see whether their HLA type is the same as yours.

There's a one in four chance of each full sibling (those who share the same parents) being an exact match.

 

Bone marrow registry

It may take several years before a suitable donor can be found. Sometimes waiting without treatment may be considered too dangerous, or finding a full match may not be possible.

In such cases, stem cells from a partially matched donor may be used. This will increase the chance of complications, but your treatment team may recommend it if the potential benefits outweigh the risks.

 

International bone marrow registers

Stages of the transplant process 

Having a bone marrow transplant is a complicated five-stage process.

The five stages are:



physical examination – to assess your general level of health



harvesting – the process of obtaining the stem cells to be used in the transplant



conditioning – preparing your body for the transplant



transplanting the stem cells



recovery period – during which you'll be monitored for any complications or side effects



The five stages are described in more detail below.

 

Physical examination

You'll have a thorough physical examination before a stem cell transplant. How healthy you are before the transplant will play a big part in your recovery.

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 of the medication used in the conditioning and recovery process can occasionally cause problems with your organs, so it's important to know how well they're functioning beforehand.

After the transplant, you'll have an increased risk of developing an infection, so it's important to make sure you don't have any underlying infections.

If you have a cancer-related condition, you may need to have a biopsy. A small sample of cancerous cells will be removed and checked in a laboratory.

The results of  the biopsy will show whether your cancer is in remission (under control) and whether there's a high risk of it returning after your transplant.

 

Harvesting stem cells

After you've had a physical examination, the stem cells will need to be harvested.

The method most commonly used in adults involves removing blood from the body, separating stem cells from the other cells in the blood and then returning the blood to the body.

An alternative method is to collect the bone marrow itself 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

It may be possible to use your own stem cells, providing they're suitable. This is known as an autologous transplantation. They can be harvested using either method described above.

If your bone marrow is being extracted, a needle will be used to remove around a litre of bone marrow. It will usually be removed from your hip bone, under general anaesthetic.

The procedure is low risk, but the area where the needle is inserted may be painful afterwards. The harvesting process may sometimes need to be carried out a number of times before enough bone marrow is obtained.

After being extracted, your stem cells may need to be treated with radiation or chemotherapy to ensure there are no cancerous cells left.

 

Allogeneic transplantation

If your own stem cells aren't suitable, stem cells will be harvested from a healthy donor. This is known as allogeneic transplantation.

In around 30% of cases, a family member, such as a brother or sister, is a suitable donor. The other 70% of people who need a bone marrow transplant have to rely on finding a suitable donor through the British Bone Marrow Registry (BBMR).

It's very important that the BBMR continues to recruit more donors, particularly from ethnic minority communities. Finding a suitable stem cell match is often difficult due to a lack of volunteers. In particular, there's a shortage of donors from African, African-Caribbean, Asian, Jewish, eastern European and Mediterranean communities.

The more people who register, 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.

The methods of harvesting cells from a healthy donor are similar to those used for an autologous transplant (see above).

For four days prior to the transplant, the donor will be given medication to stimulate the production of stem cells in their blood. On the fifth day, they'll have a blood test to check they have enough circulating stem cells.

They'll then be connected to a cell-separator machine. A general anaesthetic isn't needed, which means the harvesting can be carried out 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's 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 two to three 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's not a surgical operation, some marks from the needle will be left on the skin. There may also be some discomfort where the needle is inserted.

The donor will need to stay in hospital for up to 48 hours and have an at-home period of recovery lasting up to five days.

 

Conditioning

As part of your conditioning, you'll need to be given a range of medicines, meaing a tube will be inserted into a large vein near your heart. This is known as a central line and is used instead of many (often painful) injections.

The conditioning process involves using high doses of chemotherapy and sometimes radiation. It's carried out for three reasons:



to destroy the existing bone marrow cells to make room for the transplanted tissue



to destroy any existing cancer cells



to stop your immune system working, which reduces the risk of the transplant being rejected 



The conditioning process usually takes between four and seven days. You'll probably need to stay in hospital throughout the procedure. Side effects from chemotherapy are common and include:



nausea (feeling sick)



vomiting



diarrhoea



loss of appetite



mouth ulcers



tiredness



skin rashes



hair loss



Side effects can last for several weeks after 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, but potentially very serious, side effects of the conditioning process are lung damage and a condition called veno-occlusive disease.

Lung damage or a lung infection can be treated with oxygen, antibiotics and other treatments. Steroids (strong medication) may also be given to dampen potentially dangerous immune reactions.

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, jaundice (yellowing of the skin and whites of the eyes) and weight gain.

Veno-occlusive disease can be treated with medicines to help prevent blood clots, as well as using blood transfusions and reducing the amount of salt in your diet.

 

The transplant

It's usually possible to carry out the transplant one or two days after conditioning has finished.

The donated stem cells will be passed into your body through the central line. This process can take anywhere from half an hour to several hours to complete, depending on the type of blood cells being used.

The transplant won't be painful and you'll be awake throughout the procedure.

 

Recovery

You may feel weak after the transplant, and you may experience vomiting, diarrhoea and/or a loss of appetite.

To prevent malnutrition (a lack of essential nutrients), you'll need to have nutritional support, with high-protein fluids taken by mouth or through a tube running from 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 usually occurs 15-30 days after the transplant takes place.

During this period, you'll need to have regular blood transfusions, as you'll have a low number of red blood cells.

Your risk of developing an infection will also be increased, because you'll have a low number of white blood cells. This means that you'll need to stay in hospital, in a germ-free environment.

You may be allowed visitors, but they may have to wear surgical gowns and hats to prevent infection. Antibiotics may also be used to either prevent or treat infections.

Once engraftment has occurred, your bone marrow will begin to produce blood cells. However, you'll still be very weak from the effects of the chemotherapy.

You'll still have a high risk of developing an infection, as it can take as long as one to two years for your immune system to return to 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 between one and three months after undergoing a bone marrow transplant. However, if you develop complications, such as an infection, you may not be able to leave hospital for more than three months after the transplant.

 

Risks of bone marrow transplants

Bone marrow transplants are complex procedures that carry significant risks of serious complications.

Generally, the 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 sibling (brother or sister)



you have no serious health conditions (apart from the condition you're being treated for)



As there's a significant risk of complications occurring after a bone marrow transplant, it's important you're 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 chemotherapy (and sometimes radiotherapy), which are often needed before the transplant.

Many conditions for which a bone marrow transplant is needed 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 often occurs after stem cell transplantation.

There are two types of GvHD:



acute GvHD – which usually occurs during the first three months following 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 as a rash; the rash may later develop into blisters



a high temperature (fever) of 38°C (100.4°F) or above 



bloody or watery diarrhoea



stomach cramps



jaundice – yellowing of the skin and whites of the eyes (although this is a rare symptom of acute GvHD) 



Chronic GvHD can develop at any time between three months and two years after the transplant. The symptoms can persist or 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



hardening of the skin 



dry and sensitive mouth



dry eyes



hair loss



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 corticosteroids (see below).

Immunosuppressants stop the transplanted stem cells attacking the rest of your body. However, they'll also affect the rest of your immune system, placing you at a higher risk of infection.

Corticosteroids are powerful medications that 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 (hyperglycaemia)



increased appetite



mood changes



diarrhoea and vomiting



itchiness



high blood pressure (hypertension)



 

Infection

After having a bone marrow transplant, your risk of developing an infection will increase. This is because the conditioning you receive before the transplant will weaken your immune system. The risk of infection may be increased further if you need to take immunosuppressants.

It's 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 (pneumonia).



 

Bone marrow donor: Michelle's story

In this video Michelle talks about her experience as a bone marrow donor.


Media last reviewed: 14/11/2013

Next review due: 14/11/2015

 


Bone marrow donation

Although a bone marrow transplant can be a risky procedure, there's much less risk involved in being a donor.

To become a potential bone marrow donor you must be:



18-49 years of age to join the British Bone Marrow Registry (BBMR)



16-30 years of age to join the Anthony Nolan register



in good general health



over 51kg (8 stone) in weight



It's best to join the bone marrow register at a young age. The younger you are when you join, the more chance there is of your tissue type being matched to someone who needs it.



Bone marrow donation