Graft versus host disease

What is graft-versus-host disease?

Graft-versus-host disease (GVHD) is a condition where following transplantation the donor's immune cells in the transplant (graft) make antibodies against the patient's tissues (host) and attack vital organs. Organs most often affected include the skin, gastrointestinal (GI) tract and the liver.

Ninety per cent of bone marrow transplants lead to GVHD. Solid organ transplantation, blood transfusions, and maternal-fetal transfusions have also been reported to cause GVHD less frequently.

Types of graft-versus-host disease

There are two forms of GVHD.

• Acute GVHD
  • An early form of GVHD that occurs within the first three months of transplantation
  • The first sign is usually a skin rash appearing on the hands, feet and face
  • Gastrointestinal and liver dysfunction symptoms may follow
• Chronic GVHD
  • The late form of GVHD that develops three months post-transplantation
  • Usually evolves from acute GVHD but occurs de novo in 20-30% of patients
  • Cutaneous (skin) reactions resemble those of autoimmune disorders such as lupus, lichen planus and especially systemic sclerosis

What are the signs and symptoms of graft-versus-host disease?

Acute GVHD and chronic GVHD are distinct diseases. One common factor is that they both increase the patient's susceptibility to infection.

How is graft-versus-host disease diagnosed?

Graft-versus-graft disease may be suspected in patients who have received a transplant and develop cutaneous or systemic complications. It must be confirmed by a tissue biopsy. See graft-versus-host disease pathology for the cutaneous histological features. 

What is the treatment of graft-versus-host disease?

Patients recovering from bone marrow transplantation are usually hospitalised for several weeks following transplant and are monitored closely for signs of developing GVHD or infection. The best treatment for GVHD is prevention. This consists of a cocktail of immunosuppressive drugs such as:

• Ciclosporin
• Methotrexate
• Cyclophosphamide
• Mycophenolate
• Tacrolimus
• Sirolimus
• Prednisone.

The combination of ciclosporin and methotrexate has been found to significantly decrease the severity of GVHD. These drugs weaken the ability of the donor's immune cells to launch an attack on the patient's organs.

Treatment for patients who do develop GVHD depends on the severity of the disease. Mild cases with only skin involvement of acute GVHD may settle without treatment. More severe acute or chronic GVHD predisposes the patient to infection, and overwhelming sepsis (blood poisoning) is the main cause of death in patients with GVHD. The aim is to treat GVHD before life-threatening sepsis occurs.

• Local skin care should include emollients and topical steroids
• The vulvovaginal disease should also be managed using oestrogen cream, intravaginal corticosteroid or tacrolimus and dilators.
• High dose corticosteroids are usually added to the immunosuppressive regime.
• Targeted monoclonal antibodies such as rituximab appear very effective but are very costly.
• In 2019, ruxolitinib was approved by the Food and Drug Administration (FDA) in the US for treatment of steroid-resistant GVHD in adults and children over the age of 12 years.
• Photochemotherapy (PUVA) and high dose long-wave ultraviolet radiation (UVA1) may reduce the severity of skin problems.
• Extracorporeal photopheresis is available in a few centres and can be very effective

Because GVHD affects so many different organs, treatment is usually delivered by a multi-disciplinary team of transplant doctors, dermatologists, respiratory doctors, gastroenterologists, ophthalmologists, and other specialists.