Preventing GvHD

Graft versus host disease (GvHD) is a possible complication that can happen after a bone marrow or stem cell transplant from another person. 

Planning and treatment can help lower your risk of developing GvHD.

Drug treatment to prevent GvHD includes:

• ciclosporin
• mycophenolate mofetil (MMF)
• cyclophosphamide
• methotrexate

Getting the best donor match

GvHD can develop when the donor and the person receiving donor cells have a different tissue type.

You have a tissue typing test before your transplant. It’s also called a HLA tissue typing test.

Your transplant team look at the proteins (antigens ) that are found on the surface of most of the cells in your body. These are called human leukocyte antigens (HLA). Your doctor aims to find a donor with the closest HLA match possible.

Tissue typing

To have a tissue typing test you usually have one or more of the following tests:

• a blood test
• a swab taken from the inside of your cheek – also called a buccal swab
• a spit (saliva) sample

Doctors usually test for 5 pairs of major HLA antigens. This gives a total of 10 HLA antigens. We inherit one half of the pair from each of our parents. When choosing a donor, doctors aim to match 10 out of 10 HLA antigens. But it might be possible to do a transplant if they don't all match. These types of transplants are called mismatched transplants.

Finding a donor

Your best chance of a match is with a relative this is because we inherit the HLA proteins from our parents. You have a 1 in 4 (25%) chance of an exact match if you have a brother or sister who can donate.

Other family members can be tested if you don’t:

• have siblings
• have an unrelated donor match

Parents and adult children may be a close enough match. This is called a haploidentical transplant and means your donor is a 50% match.

Your transplant team search on a register if no one in your family is a match. The registers are of people in the general population who have volunteered to donate.

There are several including the:

• British Bone Marrow Registry (BBMR) 
• Anthony Nolan Trust register
• Welsh Bone Marrow Donor Registry
• DKMS register

Another possibility is to look at a cord blood bank register. Cord blood contains blood from umbilical cords. The mother consents to donate this when their baby is born. Doctors can use the stem cells from the cord blood.  

T cells and GvHD

Before and after your transplant, your doctor uses treatments to reduce the chance of GvHD. These treatments destroy T cells .

T cells are white blood cells that are part of the immune system . They attack cells that are foreign to the body. GvHD happens when T cells in the donated stem cells or bone marrow (the graft) attack your own body cells (the host).

So, reducing the number of T cells in the donor stem cells (the graft) reduces GvHD.

Sometimes GvHD is a good thing. The T cells in the graft also attack any remaining cancer cells. This reduces the risk of your disease coming back. This is called the graft versus disease effect. Doctors try to strike a balance between preventing severe GvHD and getting some possible benefits from mild GvHD.

To lower your risk of GvHD you might have treatment:

• before your transplant
• after your transplant

Your doctors might remove T cells from your donor’s stem cells or bone marrow.

Treatment to prevent GvHD

Your doctor gives you drugs before and after the transplant. This is to reduce the number of T cells in your stem cells or bone marrow.

Calcineurin inhibitors (ciclosporin or tacrolimus)

These medicines block the protein calcineurin. This protein is important in the causing the immune system to release cytokines into the body. When this protein is blocked it stops an immune response . This helps lower the risk of getting GvHD.

There are different types of calcineurin inhibitors and you might have them with other medicines such as chemotherapy . They include:

• ciclosporin
• tacrolimus

Chemotherapy

Preventing GvHD can include the chemotherapy drugs cyclophosphamide and methotrexate. They also help dampen down the immune system so it stops your body attacking itself.

Methotrexate

You might have a few doses of low dose methotrexate after your stem cell transplant. You have this with either ciclosporin or tacrolimus.

Cyclophosphamide

You may have high dose cyclophosphamide after your stem cell transplant. This is more likely after a half matched transplant from a family member, usually a parent or child.

You usually have this with the mycophenolate mofetil and tacrolimus.

Anti thymocytic globulin (ATG)

This medicine is also classed as a type of immunosuppressant.

This is made from human white blood cells and rabbit’s blood in the laboratory.

Donated human thymus cells are injected into the rabbit. The thymus is a small gland under the top of the breastbone. It is part of the immune system and makes white blood cells.

The rabbit’s immune system makes antibodies against the injected human white blood cells. These antibodies are then removed from the rabbit’s blood and made into the medicine ATG in the laboratory.

You usually have ATG if you have a mismatched unrelated stem cell donor. A mismatched transplant is when you have donor stem cells that partly match.

You have ATG before you have your stem cells.

Alemtuzumab (Campath)

Alemtuzumab is a monoclonal antibody (mAb) .

Alemtuzumab works by targeting a protein called CD52 on the surface of most types of white blood cells. The alemtuzumab sticks to all the CD52 proteins it finds. Then the immune system picks out the marked cells and kills them. By killing the marked cells it stops them attacking your body cells. The helps lower the chance of GvHD.

You have alemtuzumab before youhave your stem cells.

Removing T cells from the stem cells

Your doctors can remove T cells from your donor’s stem cells. This can be during or after donation and is called T cell depletion. It isn't commonly used.

Medicines in research to prevent GvHD

Researchers around the world are looking at better ways to prevent GvHD. You may have treatment as part of a clinical trial to help lower the risk of developing GvHD. Some of the research includes:

• looking at comparing standard treatment with newer combinations.
• new medicines such as sirolimus