Preventing Graft Versus Host Disease (GVHD)

Graft vs host disease (GVHD) can occur after a bone marrow or stem cell transplant. Doctors set up a program for a patient to minimise the risk of the condition developing. This incorporates HLA-matching, immune suppression and environmental conditioning.

Reducing the risk from tissue type

The closer the match between the tissue type of the donor and the host, the less the risk of the host developing GVHD. The tissue type depends on the HLA antigens in each person.

The risk regarding the tissue types depends on five pairs of HLA antigens. Half of the HLA antigens in each HLA pair comes from one of a person’s parents.  The other half in the HLA pair comes from the other parent. For identical twins, where one is the host and one is the graft, the HLA antigens in these major HLA pairs are the same and so the chance of developing GVDH is very low. Family members are more likely to have better matches. A graft from one of the patient’s parents or a sibling if possible is a preferred option.

If there is no chance of a match with parents or siblings, doctors will consider a search for other people who have as close a match in their bone marrow to the patient as possible. They may also consider tissue extracted from babies’ umbilical cords.

Suppressing the immune system

Doctors may choose to use agents that suppress the immune system of the host prior to the transplantation, such as calcineurin inhibitors (e.g. cyclosporine). These drugs are used to reduce the number of T cells in marrow or stem cells that may attack the host cells. However, these products have side effects. Cyclosporine’s unwanted effects include, among others, indigestion, elevated blood pressure, swollen gums, headaches and fatigue. Patients receive the drug through drip prior to the transplant operation. After the operation, the patient will continue to take the drug in capsule form.

Removal of T cells (T cell depletion)

This can be achieved either by in vivo or ex vivo methods. In the in vivo process, T-cell antibodies are added to the graft using an agent such as the immune suppressive antithymocyte globulin (ATG). This method lowers the risk of graft rejection. T cell depletion then happens within the patient’s body after the transplant. In the ex vivo process, T cell depletion is achieved prior to the transplant by using column absorption of ATG on the graft.

There are potential issues with both processes so researchers are still refining T cell depletion methods. Both in vivo and ex vivo processes reduce the graft-versus-leukaemia effect, meaning that the original disease has a chance of returning. Other post-transplantation lymphoproliferative disorders (LPDs) can also develop and the graft can be rejected.

Inhibition of T cell proliferation

Certain compounds can be used to inhibit the production of T cells by the graft. These include the immunosuppressant drugs methotrexate and mycophenolate. However, there are toxicity issues and the patient can develop mucositis, inflammation in their mucous regions.

Reduction intensity of conditioning processes

The doses used in chemotherapy and radiology are reduced so that some host T cells are still present. This can mean less toxicity for the patient and reduces the risk of GVHD.

Environment

The environment that the patient is treated in is also important. The risk of infection should be reduced by placing them in an environment with a low risk of infection from microorganisms.

Sunlight

The patient can also co ntribute to reducing their own risk of GVHD by staying out of the sun. UV light increases the risk of the disease. They should wear a hat, long sleeves and trousers as well as sunglasses.

Host antigen-presenting cells (APCs)

By using the blood treatment photopheresis, the process of cell death (apoptosis) is triggered in the host’s lymphocytes. Apoptotic cells are removed by the host’s antigen presenting cells, which are types of white blood cells that fight off diseases. This results in a lower chance of GVHD developing.

References

• Be the Match on preventing GVHD: https://bethematch.org/for-patients-and-families/life-after-transplant/graft-versus-host-disease/gvhd-prevention/
• Medscape on preventing GVHD: http://emedicine.medscape.com/article/886758-treatment
• Cancer Research UK on preventing GVHD: http://www.cancerresearchuk.org/about-cancer/coping-with-cancer/coping-physically/gvhd/preventing-gvhd
• Healio, High-dose cyclophosphamide may reduce severe GVHD after HSCT: http://www.healio.com/hematology-oncology/bone-marrow-transplantation/news/online/%7B2e1fbf0d-b16b-44b8-a977-77185b260953%7D/high-dose-cyclophosphamide-may-reduce-severe-gvhd-after-hsct