A look at GVHD

Graft versus host disease (GVHD) is a common complication following allogeneic (donor) stem cell transplants. It occurs in 20-80% of all stem cell transplant recipients to some degree. Most cases are mild, but it can also be a severe and life-threatening complication after transplant. Our Nurse Advisor, Fiona Heath, takes a look at the condition.

What is graft versus host disease?

Graft versus host disease (GVHD) occurs when immunologically competent donor T-lymphocytes (graft) recognise the cells and antigens in the transplant recipient as foreign and mount an inflammatory attack.

When a person has a stem cell transplant, the donor gives them a new immune system. The recipient’s own immune system will have been destroyed due to the transplant conditioning regimen. When the new stem cells engraft and grow, the donor cells (the graft) recognise the patient’s body (the host) as foreign. The new immune cells recognise the patient’s body is different to where they live, and they may attack certain organs, impairing their ability to function and increasing the patient’s susceptibility to infection. The donor cells also attack any residual malignant cells in the host’s body. This is called the ‘graft versus tumour effect’ or the ‘graft versus leukaemia effect’.

Risk Factors for GVHD

Advances in tissue typing have decreased the risk of GVHD. Risk factors for the development of GVHD include:

  • An unrelated donor
  • Older donor age (due to increased antibodies)
  • Female donor (to a male recipient)
  • If the recipient doesn’t have a very common virus called cytomegalovirus (CMV negative) but the donor is CMV positive
  • Female donors with a previous history of pregnancy
  • The use of peripheral blood stem cells can also be a risk factor for the development of chronic GVHD

There are two types of GVHD: acute and chronic. Patients may develop one, both or neither.

Acute GVHD

Acute GVHD can occur from 10 – 17 days post- transplant up until approximately three of four months post-transplant. The average time of onset is about day 25. It commonly affects the skin, the gastrointestinal tract and liver. Acute GVHD occurs in up to 50% of patients that receive an HLA (human leucocyte antigen)-identical matched sibling allograft and in up to 70% in unrelated bone marrow transplants.

Acute skin GVHD usually shows up as a skin rash that appears on the palms of hands, the soles of feet, arms, legs, chest and back. The rash usually feels itchy and dry, and in severe cases the skin may blister and peel as it would after a bad sunburn. A fever may also develop.

Acute gut GVHD most commonly occurs as diarrhoea. It is usually watery and accompanied by stomach cramps and pain. The diarrhoea can sometimes be in large volumes, up to five litres a day. Other symptoms of gut GVHD include decreased appetite, nausea and vomiting, weight loss and a sore mouth.

Acute liver GVHD is sometimes harder to diagnose. Patients will have regular blood tests to make sure their liver is working well. If the liver is affected, then the liver enzymes may be raised, and patients may become jaundiced (yellowing of eyes and skin).

Acute GVHD is graded by how severe it is. It goes from grade one, which is mild, to grade four, which is very severe. Prevention is the principle method to control GVHD. Doctors try to prevent severe GVHD from occurring by giving patients immune suppressing drugs like cyclosporin, tacrolimus and methotrexate. However, despite these drugs, GVHD occurs frequently. Once a patient exhibits evidence of acute GVHD, further treatment is initiated, usually administering steroids.

Chronic GVHD

Chronic GVHD generally occurs anywhere from three to eighteen months after transplant, although it can occur later. Chronic GVHD remains the most significant complication of an allogeneic transplant. It can affect many organs in the body. It usually affects the skin, mouth, eyes, liver, lungs, vagina, gut and joints. It may affect the body in some of the following ways:

Skin – the skin may become dry and flaky. Skin may also become tight and inflexible which may restrict movement. Patients may also develop dark or light patches of skin.

Mouth – may become dry or swollen and sometimes painful and ulcerated.

Eyes – may feel dry or gritty with some vision changes.

Gut – patients may experience diarrhoea or sensitivity to certain foods.

Sinuses – patients may feel that they have dry nasal passages or congested sinuses.

Liver – patients may have elevated levels of liver enzymes or jaundice.

Vagina – the lining of the vagina may feel dry, tight and swollen. Sex may be painful.

Penis – patients may notice some redness, a rash or ulcers on the penis.

Lungs – patients may experience shortness of breath or restricted breathing and be more prone to chest infections.

Chronic GVHD is treated with medications that suppress the immune system. These medications include cyclosporin, methotrexate, mycophenylate, tacrolimus and steroids. Patients will be on some of these drugs from ‘day zero’ of their transplant to try and prevent GVHD. Many of the same drugs are used to treat GVHD if it occurs. Topical creams and ointments may also be used to treat skin, oral and vaginal GVHD. Other treatments include Ultraviolet phototherapy, intravenous immunoglobulin (IVIG) and T-cell depletion, in which T-lymphocytes are removed from the stem cell graft.

The prospect of GVHD can be frightening to many patients. Patients who go on to develop GVHD may become depressed, angry or anxious, seeing the disease as another setback that will delay their recovery. It is important to remember that in most cases GVHD is mild or moderate and that both the effects of the disease and side effects of drugs used to treat it are only temporary.

Examples of Jack’s Acute and Chronic skin GVHD. You can read Jack’s story, written from the perspective of his mom Tracey here.

Jack Warboys’ experience

Here, Tracey Warboys talks about her son, Jack’s, experience of acute and chronic GVHD.

My son Jack was just eight and a half when he had a sibling bone marrow transplant (his older brother Lewis was his 10/10 match) in June 2015 after he relapsed only 13 months from diagnosis and into treatment for T-cell acute lymphoblastic leukaemia (T-ALL).
Jack had quite a few issues after the transplant, including cyclosporin and tacrolimus toxicity of the kidneys and liver, steroid-induced high blood pressure and acute skin GVHD.

We were told that skin GVHD is more or less expected after the transplant, which is particularly good for helping to get rid of any remaining leukaemia cells that may be in the body still. However, if it was to continue after the first 100 days post-transplant, it could become an issue.
Jack’s skin was often extremely red and itchy after engraftment, and we were told it was GVHD. His skin GVHD was classed as acute stage three, not reducing in activity whilst on high dose of steroids or immunosuppressive treatment. He was on high dose steroids to start with, but his consultant decided to wean him off them after about a year and a half post-transplant, as his skin, although still active with GVHD, seemed to be stable and looked much better. Unfortunately, this was short lived as his skin flared up so much after only a few weeks off the steroids that he had to go back on the high dose again.
Jack’s skin was now classed as chronic. His skin was a lot more red and itchy, it was also very scaly, and he now had areas on his chest, neck and backs of his upper arms that had actually split and became very sore. We were told that the skin GVHD was really bad and that the best way to try and help reduce the activity was for Jack to have ECP treatment (photopheresis).

Jack started his treatment in June 2017 (two years post-transplant). He has ECP every fortnight on two consecutive days (Wednesday and Thursday) at Birmingham Children’s Hospital. He has a Hickman line so that the infusion is easier as it can take up to three hours. We have seen a big difference in his skin; it’s not as itchy or red, the scaly patches are now smooth and almost back to his normal skin colour. It is a slow but steady progress, especially since Jack’s skin and underlying tissue have been affected by Scleroderma, which has also affected his mobility and straightening of his arms.

He has had to have 4×1 a week infusions of rituximab to help, along with physiotherapy. Fortunately, he has responded well to the ECP and rituximab, so things are going OK at the moment. We don’t know how long Jack will need the ECP treatment for, it all depends on how his GVHD is. We were told he could have treatment for six months or it could be two years plus, (we are now approaching a year since treatment began); we really don’t know. He is still on steroids, albeit a very low dose, which we hope to reduce and eventually stop. Again, this depends on the ECP treatment.

Jack’s skin and underlying tissue have been the only things affected by GVHD, thankfully. Unfortunately, GVHD can affect other parts of the body like the liver, the eyes and the gut. These are often very serious and are unfortunately a big part of having a transplant.


Allogeneic stem cell transplant

  • A transplant in which the donor stem cells come from a specifically matched donor. More information can be found in our information booklet here.

Conditioning regimen

  • Therapy (chemotherapy and/or radiotherapy) designed to completely destroy a bone marrow transplant patient’s bone marrow in preparation for transplant

Cytomegalovirus (CMV)

  • A type of virus that is usually not harmful in healthy individuals but can cause problems, especially pneumonia, in people with a low resistance to infection

Human leucocyte antigen (HLA)

  • A special marker found on the white blood cells. HLA tissue typing is done to determine whether recipient cells and potential donor cells match


  • A yellowish skin colour. There is usually some damage to the liver if you are this colour


  • A person who receives transplanted bone marrow

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