Graft-versus-host disease

Dr Sharlene Parasnath explains what graft-versus-host disease is in regard to allogeneic haematopoietic stem cell transplantation.

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Allogeneic haematopoietic stem cell transplantation (HSCT) has the potential to cure life-threatening blood cancers and other blood and bone marrow disorders, including leukaemia and aplastic anaemia. However, there are various complications that may be associated with HSCT.

Graft-versus-host disease (GVHD) is a potentially serious complication of allogeneic haematopoietic stem cell transplantation. During allogeneic stem cell transplantation, a patient receives stem cells from a donor. 

GVHD occurs when the donor’s T lymphocytes (the graft) identifies the patient’s healthy cells (the host) as foreign, and attacks them, resulting in damage to cells and tissues of the body.

Prevention

Patients undergoing allogeneic stem cell transplantation receive treatment to prevent GVHD. This includes immunosuppressive drugs which suppress the T-cells in the graft, to prevent them attacking the patient’s cells. T-cells may also be removed from the graft prior to infusing the cells. Treatment practices may vary depending on protocols used in different centres performing haematopoietic stem cell transplantation.

Two types of graft-versus-host disease

GVHD has been classified into acute and chronic. Each type affects different organs and tissues and has different signs and symptoms and the grades range from mild to severe. Patients may develop one type or both.

Acute GVHD 

This develops within the first 100 days following transplantation but can occur later. It can affect the skin, gastrointestinal tract or the liver. Symptoms may include rash and redness of the skin with involvement of the palms and soles of the feet and often involve the trunk and other extremities as well. The skin may blister, and in severe cases can flake. 

Patients with GVHD of the gastrointestinal system may complain of nausea, vomiting, abdominal cramps, loss of appetite and diarrhoea. Yellowing of the eyes (jaundice) may be a sign of possible GVHD of the liver.

Chronic GVHD 

Chronic GVHD tends to be more complicated than acute GVHD and generally occurs 100 days following HSCT. It also affects the skin, gastrointestinal tract and liver, however, often involves other organs and systems including hair, nails, liver, lungs, muscles, joints, eyes and genitourinary system. Symptoms will depend on the organ or system affected.

Dryness of the mouth and ulcers that may extend down to the throat may result in pain and difficulty eating and swallowing. Patients may complain of thickening and tightening of the skin, resulting in restriction in joint mobility. Changes in skin colour and intolerance to temperature changes due to damage to sweat glands may occur. Nail changes include hard, brittle nails and nail loss. Patients may report hair loss on the head and body and premature greying of the hair.

Unexplained weight loss, loss of appetite, nausea, vomiting, diarrhoea and abdominal pain may occur in GVHD of the gastrointestinal tract. 

Patients with GVHD of the lungs may report shortness of breath, difficulty breathing, persistent cough or wheezing. Muscle weakness and cramps or joint stiffness causing difficulty in fully extending joints of fingers, wrists, elbows, knees or ankles may occur. 

The genitalia may be affected. Females may report vaginal dryness; itching; pain; ulcerations, scarring and narrowing of the vagina. In men, narrowing or scarring of the urethra, itching or scarring on the penis and scrotum may occur.

Treatment

After transplantation, patients usually continue the immunosuppressive drugs which may include cyclosporine, tacrolimus or methotrexate to prevent GVHD.

Many patients who develop acute GVHD are often successfully treated by increased immunosuppression in the form of corticosteroids such as prednisone. Patients with mild acute GVHD of the skin usually respond well to the oral immunosuppressive treatment and topical steroids to the affected areas.

Severe acute GVHD and chronic GVHD with systemic manifestations treatment requires increasing systemic immunosuppressive agents and adding a corticosteroid. Other treatment modalities in patients not responding to corticosteroids include ruxolitinib and non-pharmacological modalities such as photopheresis (removes blood via a machine and isolates white blood cells).

It’s important for patients, caregivers and healthcare professionals to be aware of the warning signs of GVHD. 

Please contact the treating centre immediately if any symptoms appear as early detection and treatment may help limit the severity of the disease.  

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