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About graft versus host disease (GVHD)

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This page tells you about graft versus host disease (GVHD). You can find out about

 

What GVHD is

GVHD is a possible complication of high dose cancer treatment. It happens after a bone marrow or stem cell transplant from another person. This is called a donor transplant or an allogeneic (aloe-gen-ay-ik) transplant. Bone marrow and stem cell transplants are treatments that use very high doses of chemotherapy, sometimes with radiotherapy. The high dose treatment can kill cancer cells but it also kills off the stem cells in your bone marrow that produce your blood cells. So after the high dose treatment you have stem cells or bone marrow from your donor through a drip. The donor stem cells make their way into your bone marrow and start to produce blood cells again. 

GVHD happens when particular types of white blood cell (T cells) in the donated bone marrow or stem cells attack your own body cells. This happens because the donated cells (the graft) see your body cells (the host) as foreign and attack them.

It is difficult to say who will develop GVHD after a transplant. We don’t know exactly, but somewhere between 1 and 4 out of every 5 people (20 to 80%) having a donor transplant will develop some degree of GVHD. Some people have a very mild form which doesn’t last long. For others, GVHD can be severe. It may even be life threatening in a few cases. Some people may have GVHD over many months, or even years.

 

How GVHD develops

GVHD happens because the transplant affects your immune system. The donor's bone marrow or stem cells will contain some T cells. T cells are a type of white blood cell that help us fight infections. T cells attack and destroy cells they see as foreign, and potentially harmful, such as bacteria and viruses. Normally T cells don’t attack our own body cells, because they recognise proteins on the cells called HLA (human leukocyte antigens). We inherit our HLA from our parents. Apart from identical twins, HLA is unique to each person.

Before a bone marrow or stem cell transplant, you and your donor have blood tests to check how closely your HLA matches. This test is called tissue typing. If you and your donor have very similar HLA this lowers the chance of GVHD. The more differences there are between your HLA and your donor's, the more likely you are to get GVHD.

After a transplant your bone marrow starts making new blood cells from the donor stem cells. These new blood cells have the donor's HLA pattern. They recognise the HLA pattern on your body cells as different (foreign) and may begin to attack some of them. The GVHD may affect different areas of your body. Most commonly it affects the

  • Skin
  • Digestive system (including the bowel and stomach)
  • Liver
 

Possible benefits of GVHD

The symptoms of GVHD can be difficult to cope with, and in some cases GVHD is a serious, even life threatening, problem. But if you are having a transplant, having mild GVHD may be a good thing. As well as attacking your body cells, the donor T cells will also attack any remaining cancer cells. Doctors call this the graft versus disease effect. The graft means the donor T cells.

 

Types of GVHD

GVHD can be grouped according to when it starts after your transplant. Doctors also look at what parts of the body are affected and how badly, and the biopsy results. GVHD can be divided into

Acute GVHD

Acute GVHD is also called fulminant GVHD. It generally starts within 100 days of your transplant. But it can sometimes happen after this time. Acute GVHD can be mild or severe. It starts after your new bone marrow begins to make blood cells. Doctors call this engraftment and it usually happens about 2 to 3 weeks after your transplant. 

Acute GVHD often starts with a rash on the palms of your hands and soles of your feet, your ears or face. The rash may be itchy or painful. Acute GVHD may also affect your mouth, gut (digestive system) and liver. This can cause diarrhoea, sickness, loss of appetite, and yellowing of the skin (jaundice).

Chronic GVHD 

Chronic GVHD starts more than 100 days after your transplant. You are more likely to get it if you have had acute GVHD. But it can happen even if you haven't had acute GVHD. 

Like acute GVHD, it may affect your skin, gut, liver or mouth. But it can also affect other parts of your body, such as your eyes, lungs, vagina and joints. Chronic GVHD may be mild or severe, and for some people can go on for several months or even years.

Late acute GVHD and overlap syndrome

The National Institutes of Health classification includes late acute GVHD (starting after day 100) and an overlap syndrome with features of both acute and chronic GVHD. They are both more likely to happen after mini transplants (reduced intensity conditioning), which doctors now use more often.

 

Risk factors for GVHD

A number of factors can increase your risk of GVHD. These include the following

Unrelated donor transplants

If your donor is not related to you, your risk of developing GVHD is greater than if your donor is a brother or sister (sibling).

Mismatched donors

If you have a mismatched transplant your donor will be as close an HLA match as possible. But sometimes the best available bone marrow donor is still a slight mismatch. This increases the risk of GVHD.

High numbers of T cells in the donated stem cells or bone marrow

Donated stem cells or bone marrow that contain high numbers of T cells are more likely to cause GVHD. This is called a T cell replete stem cell transplant. Whilst this type of transplant may cause more GVHD, it may also lower the chance of relapse. 

Age

The older you and your donor are, the greater your risk of developing GVHD.

Having a donor of a different sex to you

If your donor is a different sex to you, the risk of GVHD is slightly increased. This is particularly true if a male has a female donor who has had children or been pregnant in the past.

Testing positive for cytomegalovirus (CMV)

Cytomegalovirus (pronounced sy-toe-meg-aloe virus) is also called CMV. It is a very common virus that is usually harmless. Over 6 out of 10 people (60%) in the general population test positive for CMV. In other words, they have CMV antibodies in their blood. If you are CMV negative but your donor is positive, your risk of GVHD is higher.

Donor lymphocyte infusion (DLI) for disease that has come back

Nowadays doctors are able to treat people whose disease has come back following a donor transplant. They use a treatment called donor lymphocyte infusion (DLI), using white blood cells from the donor. The idea is that the donor’s cells will attack the disease (the graft versus disease effect). But this is very likely to cause some GVHD.

 

Balancing the benefits and disadvantages of GVHD

GVHD can be unpleasant and reduce quality of life. In severe cases it can be life threatening. But mild GVHD can lower the chance of leukaemia or lymphoma coming back (relapse). There are treatments to prevent GVHD. Doctors fine tune the use of these treatments. They try to lower the risk of serious GVHD as far as possible, but still keep some benefits of GVHD. This may help to stop the disease coming back.

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Updated: 20 November 2014