Drugs used for treating GVHD
This page tells you about the drugs used to treat graft versus host disease (GVHD). There is information about
- How the drugs work
- Anti lymphocytic or anti thymocytic globulin (ALG or ATG)
- Monoclonal antibodies
- Mycophenolate mofetil (MMF)
- Pentostatin (Nipent)
Most of these drugs work by damping down your immune system and so stopping the donated cells attacking your body. If you have GVHD, you are at a greater risk of getting an infection because it weakens your immune system. Treatments for GVHD further increase this risk. Your doctor and nurses will keep a close eye on you, but you should report any signs of infection as soon as you notice them, so you can start any necessary treatment.
Although steroids are made naturally in the body they can also be made artificially and used to treat various conditions. Steroids suppress your immune response and reduce inflammation. The most common types of steroids used for GVHD are prednisolone, which you take as a tablet, and methylprednisolone which you usually have as an injection into a vein. You can find out about the side effects of steroids in our section about cancer drugs.
Steroids are available as creams to reduce skin GVHD. They are also available as eye drops if you have GVHD affecting the eye.
Once your GVHD is under control, your doctor will gradually reduce the dose. You might have steroids on their own, or with one of the other drugs or treatments listed here.
Ciclosporin is also known as Neoral, Deximune, Sandimmum. This drug works by reducing the number of T cells in your body. It comes as a capsule which you take daily or as a liquid that you drink. You must not have grapefruit or grapefruit juice within an hour of taking ciclosporin because it can interfere with how the drug works. You will have regular blood tests to check for side effects to your kidneys or liver.
The main side effects of ciclosporin are
- Nausea and indigestion
- Raised blood pressure
- Low levels of red blood cells (anaemia)
- Shaking hands (tremor)
- Kidney problems
- Excess growth of body and facial hair in women (hirsutism)
- Gum enlargement
Tacrolimus is also known as Prograf, Modigraf and Advagraf. It suppresses your immune system to treat GVHD. It comes as capsules which you usually take twice a day It is also available as a liquid that you drink. You can also have it by drip (intravenously).
The main side effects are
- Shaking hands
- High blood sugar
- Nausea and loss of appetite
- Stomach pain
- Difficulty in sleeping
Your doctor may prescribe Protopic ointment (tacrolimus) if you have GVHD affecting the eyes.
This drug destroys T cells. Doctors sometimes use it before transplant to prevent your body rejecting the donor cells and reduce your risk of GVHD. But you might also have ATG or ALG if you develop GVHD. You have it as a drip (infusion) over about 4 hours.
You may react to this drug. It may cause symptoms such as fever, shakiness, skin rash, sickness, headache and changes to your blood pressure. Your nurse will probably give you medicines beforehand to to help prevent a reaction.
Monoclonal antibodies are made in the laboratory and are designed to target specific proteins on the surface of body cells. You have them through a drip (intravenously) into your bloodstream.
Several types of monoclonal antibody are being used to treat GVHD. There is information here about
- Alemtuzumab (Campath)
- Daclizumab (Zenapax)
- Infliximab (Remicade)
- Rituximab (Mabthera)
- Possible side effects of monoclonal antibodies
Alemtuzumab works by targeting a protein on the surface of certain white blood cells and destroying them. This suppresses your immune system and helps prevent or treat GVHD.
Daclizumab targets a receptor on T cells, making them inactive. This receptor is more common on T cells that are activated, as they are in GVHD.
Infliximab has been used to treat acute GVHD. It targets a type of chemical called a cytokine, which causes inflammation of body tissues. Infliximab binds with the cytokine to stop it from working.
Rituximab acts on white blood cells called B cells. We still don’t completely understand how GVHD develops. In the past doctors thought only the T cells were involved. Over the last couple of years they have been looking at whether B lymphocytes (another type of white blood cell) might also be involved. These lymphocytes make antibodies which destroy foreign cells. Doctors have found that giving rituximab may help treat chronic GVHD. But we need more research to confirm this.
Treatment with any monoclonal antibody can make you more prone to infections. So, as with GVHD generally, look out for any signs of infection and report them immediately to your doctor. The most common side effect of all monoclonal antibodies is an allergic reaction to the drug. This reaction is most likely to happen when you first have the treatment. You will have paracetamol and an antihistamine drug before you have the treatment to prevent a reaction. If you have a reaction, your doctor or nurse can usually control it by slowing down or stopping the drip for a while.
You can find out about the general side effects of monoclonal antibodies in the biological therapy section. You can find information about the side effects of individual biological therapy drugs in the cancer drugs section.
Mycophenolate is also known as CellCept. It is another drug used to damp down your immune system. You take it by mouth as a tablet, capsule or liquid, usually twice a day. The main side effects are diarrhoea, sickness and a higher risk of infections because it lowers your white blood count.
Pentostatin (Nipent) is a chemotherapy drug which can be used against acute or chronic GVHD because it breaks down the harmful T cells. You have it through a drip in your arm (intravenously). This drug puts you at a higher risk of infections. So, as with GVHD generally, look out for any signs of infection and report them immediately to your doctor. You can find information about pentostatin in the cancer drugs section.
This is also known as extracorporeal therapy or light therapy. Photopheresis can improve skin, liver and mouth GVHD. Your doctor may also suggest it for chronic GVHD of the lung.
Doctors normally give photopheresis after other treatment hasn’t worked or has stopped working. Photopheresis is a complicated process and it may take up to 6 months before you see any real improvement in symptoms. If your doctors think photopheresis may help treat your GVHD, they will refer you to a skin specialist (dermatologist) at a centre that offers this treatment.
To have the treatment your nurse will connect you to a machine by a drip. Your blood then goes through the machine, which separates off some of your white blood cells. You then have your blood, minus the white blood cells, given back into your vein. The separated white blood cells are treated with a special drug and then exposed to ultraviolet light. This light activates the drug so that it is able to destroy the abnormal white blood cells. After this process your nurse gives back the treated white blood cells into your vein.
Each treatment takes between 3 and 4 hours, and you would usually have it every 2 weeks for between 6 and 12 months. Having this procedure does not hurt, but you will usually need to have a central line. Some people may feel a bit weak or dizzy during or after the treatment. After the treatment your skin and eyes may be more sensitive to sunlight for about 24 hours, so you need to protect yourself from the sun and wear sunglasses.
PUVA ( Psoralen Ultra Violet A) is photochemotherapy (another type of light therapy). You usually have PUVA if other treatments haven’t worked or are no longer working. Research has shown it can help with chronic GVHD affecting the skin.
This method involves a drug called psoralen, which you take as a tablet before the light treatment. You then go into a room to have the light treatment. You will need to wear sunglasses and a barrier cream for your lips. Treatment is usually 3 times a week.
Your skin and eyes will be sensitive to light for about 24 hours after each treatment. You should wear sunglasses and protect your skin.
Narrow band ultraviolet B (NB-UVB) is also a light therapy, but unlike UVA treatment does not need the drug psoralen to make the skin sensitive to light. A small study in Italy showed that NB-UVB can help as a second line treatment for children who have GVHD of the skin. A study in the US is looking to see if NB-UVB helps chronic GVHD of the mouth.
Azathioprine is also known as Imuran. This is another drug that damps down the immune system. You are most likely to take it by mouth. Very rarely, if you are too unwell to take drugs by mouth you may start by having azathioprine as a drip into a vein (intravenously). The main side effect is an increased risk of infections.
Thalidomide is a type of biological therapy. It has been tested as a treatment for GVHD. Some research has shown that it can help to control chronic GVHD. It is not used very often and usually only if other treatments are not controlling the GVHD. You take thalidomide as a tablet. The main side effects are drowsiness, constipation and numbness of the fingers or toes and an increased risk of blood clots. It is also essential to avoid pregnancy. There is information about the side effects of thalidomide in the cancer drugs section.
Sirolimus is an immune suppressor drug that trials have shown can help to prevent GVHD. It may also be used to treat severe acute GVHD. It can also sometimes help to control chronic GVHD when steroids and ciclosporin are not working. You take it as tablets or a solution that you drink. You must not have grapefruit or grapefruit juice within an hour of taking sirolimus because it can interfere with how the drug works. Rapamune liquid contains soya oil. Patients allergic to peanut or soya must not take this medicine. You will have regular blood tests to check your liver and kidney function.
The possible side effects include
- Low levels of platelets or red blood cells
- A high temperature
- High blood pressure
- Low levels of blood potassium and phosphate
- Abdominal pain, diarrhoea or constipation
Sirolimus is a new drug and doctors are still working out the best ways to use it. It can be combined with other drugs that suppress immune function.
Newer drugs being used for GVHD include
- Everolimus – a biological therapy
- Imatinib – a biological therapy
- Clofazamine (Lamprene) – a drug usually used to treat the skin condition leprosy
- Halofuginone – a drug that prevents the development of T cells and reduces inflammation
- Etanercept – it blocks the production of tumour necrosis factor and can help reduce skin GVHD
- Hydroxychloroquine – this is a drug usually used to treat malaria
- Etretinate – a drug usually used to treat the skin condition psoriasis
These drugs are all in the early phases of research for GVHD. It is not yet known how well they work. Your doctor may offer you one of these treatments if other treatments have not controlled your GVHD.
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