graft-versus-host disease (gvhd): signs, prevalence and clinical guidelines for treatment in canada
graft-versus-host disease develops when foreign cells are introduced into the body and cannot recognize the cells they interact with within the host.
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according to research, roughly 1,500 people developed chronic gvhd in canada in 2021. more data shows that, for people who develop gvhd, the mortality rate sits at approximately 17 to 20 per cent.
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graft-versus-host disease is not a disease in itself but rather a complication that can occur following a specific stem cell transplant, known as an allogeneic transplant. these procedures are typically conducted in patients with conditions such as leukemia, lymphoma, or aplastic anemia that require stem cells to replace or repopulate the blood with healthy cells.
when an allogeneic transplant is performed, a donor’s immature blood cells (stem cells) are injected into the body. the cells are left to grow into healthy, mature cells to help correct deficiencies or issues within the blood. in some cases, upon entering the body, donor cells perceive the existing cells as foreign and begin to attack them.
donated stem cells are referred to as grafts, whereas the recipient’s own cells are referred to as the host, giving rise to the term graft-versus-host disease.
types and signs of graft-versus-host disease
there are two types of gvhd: acute and chronic. the acute version occurs within 100 days of the transplant, whereas chronic can happen at any time after the transplant, typically showing signs within the first two years. people can experience one or both types of gvhd after a transplant, but many do not develop the condition at all.
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the symptoms of gvhd can range from mild to fatal and vary depending on the type. for acute gvhd, the symptoms can include:
- a sunburn-like rash that is itchy, painful, and red and starts on the shoulders, neck, ears, palms of the hands, and soles of the feet. the rash can spread to cover the entire body.
- blisters and peeling of the skin
- gastrointestinal upset, including diarrhea, nausea, vomiting, and abdominal cramping
- yellowing of the skin or eyes, a condition known as jaundice and other liver complications, such as an enlarged liver, liver tenderness, liver failure, or abnormal liver enzymes
chronic gvhd will present with all the same symptoms mentioned above, but more signs of the condition may also be present, such as:
- hair loss from the head and body
- swelling and tightness of the skin
- oral issues, including dry mouth, mouth sores, and gum disease
- changes in vision or dry and gritty feeling in the eyes
- respiratory symptoms, including shortness of breath and a dry and persistent cough
- muscle and joint ailments, such as weakness, cramping, or pain in the muscles and a decreased range of motion
- sexual health complications, including vaginal dryness, itchiness in the vaginal, penile, or scrotal area, and pain during intercourse
- infections
- unintended weight loss
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chronic gvhd is more likely to cause more severe complications in those who develop it, and this type is often associated with worse health outcomes, impairment, and reduced quality of life. some possible complications of chronic gvhd include:
- chronic pain
- fatigue
- bone density loss
- hyperlipidemia
- high blood sugar
- joint stiffness
- persistent gastrointestinal upset
the cause of graft-versus-host disease
gvhd develops when foreign cells are introduced into the body and cannot recognize the cells they interact with within the host. this is because each cell in the body contains an identifier protein known as human leukocyte antigens (hla). these proteins are designed to show other cells that they belong.
as the stem cells donated begin to mature, their hla protein will resemble that of the donor’s cells, and if the difference is too obvious to the donated blood cells, they will mark the new cells as threats.
healthcare providers aim to find donors that have hla as similar as possible, but it doesn’t always work, and gvhd develops. those at the highest risk of developing gvhd include people who receive donated cells from someone who has been pregnant in the past, either the donor and/or recipient are older in age, a recipient gets cells from someone of the opposite sex, or donor cells are taken from the bloodstream as opposed to bone marrow.
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if a person receives donor cells from someone who is related to them but the hla isn’t a match or from a person who is not related but is an hla match, they are at the highest risk of developing gvhd.
graft-versus-host disease prevalence in canada
the incidence rates of gvhd in canada are somewhat high, and as many as 30 to 50 per cent of people who undergo an allogeneic transplant will develop gvdh. in the case of acute gvhd, roughly half of patients who receive cells from an unrelated donor and one in three patients who receive cells from a related donor will develop the condition.
chronic gvhd is less likely but can be more severe. according to research, roughly 1,500 people developed chronic gvhd in canada in 2021. more data shows that, for people who develop gvhd, the mortality rate sits at approximately 17 to 20 per cent.
clinical guidelines for treating graft-versus-host disease in canada
prevention and treatment are of the utmost importance for people who require stem cell transplants, which can lead to gvhd. in some cases, medical providers examine the donor cells and remove the ones they believe could cause an issue. people receiving the transplant may also be given immunosuppressant medications that can hinder the immune system’s overreaction, preventing or treating gvhd in the process.
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drugs that are commonly used together in the prevention and treatment of gvhd are cyclosporine and methotrexate. other drugs that may be used include:
- prednisone
- tacrolimus
- mycophenolate
- sirolimus
- thalidomide
- azathioprine
- pentostatin
- infliximab
- dacluzimab
- ibrutinib
- antifungals, antibiotics, and antivirals to reduce infection risk
- eye drops for eye symptoms
to ensure a person who develops gvhd is treated quickly, healthcare providers will monitor for symptoms of gvhd following an allogeneic transplant.
clinical guidelines released in 2024 recognize the need for a multidisciplinary approach to treating and managing gvhd in patients for the best possible outcomes. the main goals of treatment are addressing symptoms and reducing complications. in addition to medical treatment, psychological and social support may also be provided to people with gvhd.
other possible routes that can be taken to address all symptoms and complications include physiotherapy, exercise, pain reduction techniques and medications, and specialist care that matches the ensuing comorbidities that can develop.
living with graft-versus-host disease
people living with gvhd, especially chronic, will experience a reduced quality of life and a significant burden of having to care for themselves and their symptoms. typically, their daily activities and their ability to work and socialize with others will be disrupted.
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to ensure those who develop gvhd retain the highest quality of life possible, medical care teams must act quickly and address symptoms and complications with the proper medications and therapies.
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