People being treated for certain cancers may undergo a stem cell transplant. Graft-versus-host disease (GVHD) is a complication that may happen when the donor cells attack the recipient’s healthy cells.

An allogeneic transplant is a procedure that involves using cells collected from a cancer-free donor who matches the recipient’s tissue type. These healthy cells are used to replace cells that were destroyed during radiation or chemotherapy. The donor is usually a close relative, such as a sibling.

Using a donor for stem cell transplants offers what is called a “graft-versus-cancer effect,” in which the donor’s stem cells (graft) may attack any cancer cells found in the recipient (host).

However, it can also cause a condition called graft-versus-host-disease (GVHD).

GVHD is a serious and potentially life threatening condition in which the donor cells attack the recipient’s healthy cells, causing a range of health issues.

In this condition, the donor’s T cells (the graft) do not recognize the host’s healthy cells, so they attack them.

A person can develop GVHD for several reasons. If the donor is human leukocyte antigen (HLA) mismatched, the recipient may have a higher risk of developing GVHD. This is discussed in more detail below.

There are two types of GVHD: acute and chronic.

Acute GVHD

It is hard to say exactly how often acute GVHD occurs, but approximately 30–70% of people who undergo an allogeneic transplant develop GVHD, reports the Leukemia and Lymphoma Society.

Acute GVHD is diagnosed within the first 100 days following an allogeneic stem cell transplant, most commonly occurring within the first 2–3 weeks following the procedure.

During this time, the new bone marrow begins to make new blood cells, and the donor’s immune cells start to attack the recipient’s healthy cells.

Acute GVHD can affect the skin, liver, and gut. It can cause various symptoms, such as skin rashes, diarrhea (sometimes with stomach pain and vomiting), or an increase in liver enzymes. Some people will go on to develop chronic GVHD.

Chronic GVHD

Chronic GVHD most commonly occurs in people who have experienced acute GVHD. It can occur anywhere from 3 months to over a year following a stem cell transplant. Cases of chronic GVHD can range from mild to severe. They can be long lasting and debilitating.

Chronic GVHD can lead to skin problems and hair loss. It can also damage organs, such as the lungs and liver.

Chronic GVHD can have different effects on many parts of the body:

  • Skin: skin rashes and changes, such as drying, scaling, scarring, hardening, and darkening
  • Joints: restricted motion due to skin scarring
  • Hair: hair loss
  • Mouth: ulcers in the lining of the mouth and the food pipe due to membrane dryness
  • Eyes: loss of tears, redness, and irritation
  • Genitals: vaginal dryness, stenosis
  • Lungs: scarring and dryness
  • Liver: liver damage and failure, jaundice

Acute GVHD typically leads to a skin rash affecting the palms of the hands, soles of the feet, ears, or face. People may experience pain or itching with these skin rashes. This rash can spread to the trunk of the body.

Other common symptoms include:

  • skin burning and redness
  • skin blistering and flaking
  • diarrhea
  • nausea and vomiting
  • stomach cramping
  • loss of appetite
  • stomach and intestinal bleeding
  • yellowing of the skin or whites of the eyes, indicating liver damage
  • digestive tract ulcers from mouth and throat dryness
  • lung, vaginal, and other membrane dryness
  • shortness of breath
  • weight loss
  • reduced joint mobility
  • hair loss
  • eye irritation and redness
  • visual changes
  • loss of tear production
  • tiredness
  • chronic pain
  • muscle weakness

Doctors will discuss in detail any symptoms that should be reported to them for immediate care and treatment.

Diagnosis

Doctors can diagnose both acute and chronic GVHD after an evaluation of symptoms. However, a biopsy of a tissue sample will confirm the condition.

A healthcare professional may take a biopsy from the skin, liver, stomach, intestine, or other sites to get an accurate diagnosis. Doctors may recommend other tests as necessary.

GVHD is an immune response to a foreign body. In the case of GVHD, the foreign body is not the donor cells but the cells of the person receiving the transplant.

Donor T cells, which are white blood cells responsible for fighting infection, do not recognize the host’s cells in whichever organ is affected after receiving a stem cell transplant.

Tissue damage caused by the treatment the recipient is receiving leads to the release of inflammatory proteins. These proteins increase the expression of substances within the recipient’s cells that stimulate the immune cells.

In turn, this leads to the activation of donor T cells against the cells of the recipient. The immune response is mediated by the T cells of the host. As target cells die and tissue is destroyed by the immune reaction, a greater inflammatory response occurs.

All people have a unique protein that is inherited from both parents, called human leukocyte antigen (HLA). The only people with identical HLA are identical twins.

In an attempt to prevent GVHD from occurring, donors and recipients are HLA-matched before the transfusion to be sure their HLA matches as closely as possible.

HLA-matching does not always work, however. There is always a risk of GVHD with allogeneic stem cell transplants.

The chances of GVHD occurring increase under some circumstances, such as when:

  • the recipient is not a blood relative of the donor
  • there is a donor HLA mismatch, even if only slightly
  • donor stem cells have high T cell counts
  • the donor is older in age
  • the donor is of a different sex, especially if the donor is female and the recipient is male
  • the donor has cytomegalovirus (CMV) and the recipient does not
  • the recipient is receiving white blood cells from a donor

Healthcare professionals use medications to suppress the immune system or anti-inflammatory medications, such as steroids, to treat GVHD. The choice will depend on whether the condition is acute or chronic.

People with GVHD may require treatment for up to 1 year and beyond, depending on how they respond to therapy.

Classes of medication called glucocorticoids (steroids) and cyclosporine (immunosuppressive drugs) typically treat acute GVHD.

Additional medications that have either been newly approved or are undergoing evaluation in clinical trials include:

  • antithymocyte globulin (rabbit ATG; Thymoglobulin)
  • denileukin diftitox (Ontak)
  • intra-arterial corticosteroids
  • monoclonal antibodies, such as:
    • basiliximab (Simulect)
    • daclizumab (Zenapax)
    • infliximab (Remicade)
    • more rarely, alemtuzumab (Campath)
  • mycophenolate mofetil (CellCept)
  • oral non-absorbable corticosteroids, such as budesonide or beclomethasone dipropionate
  • pentostatin (Nipent)
  • sirolimus (Rapamune)
  • tacrolimus (Prograf)

Another potential form of treatment is extracorporeal photopheresis. It is a procedure that removes, treats, and reinfuses the patient’s blood. Infusions of mesenchymal stem cells are currently under trial.

A class of steroids called corticosteroids, and possibly cyclosporine, typically treats chronic GVHD. Other medications are available if the condition is not responding to traditional therapy. These include:

  • daclizumab (Zenapax)
  • etanercept (Enbrel)
  • imatinib mesylate (Gleevec) for some skin changes
  • infliximab (Remicade)
  • mycophenolate mofetil (CellCept)
  • pentostatin (Nipent)
  • tacrolimus (Prograf)
  • thalidomide (Thalomid)

Can GVHD be permanently cured?

With proper treatment, many cases of both acute and chronic GvHD can be successfully cured. However, some cases may last a lifetime and cause damage to the lungs, liver, and other organs.

People with GVHD can check in regularly with their doctor to monitor the effectiveness of their treatment and any potential side effects.

GVHD can range from mild to severe and can be life threatening in some cases. Doctors will discuss a person’s outlook individually. A person’s outlook is based on several factors, like when the disease was detected, the severity of disease, and response to treatment.

It is important to note that GVHD is a complex disease. A doctor will consider all possible treatment options when discussing outlook and forming an overall care plan.

Is GVHD fatal?

In severe cases, GVHD can be fatal. Symptoms of GVHD affecting the lungs and musculoskeletal system can be life threatening. This is why it is important to seek treatment to prevent its progression.

However, a 2019 study found that survival rates have improved in recent years due to better treatment methods and care practices. Now, more than 2 in 3 people with severe GVHD survive 2 years after the onset of disease.

Graft-versus-host disease (GVHD) is a serious and potentially life threatening condition in which donor cells attack the recipient’s healthy cells after a stem cell transplant. GVHD can appear in an acute or chronic form. It can cause a range of medical problems.

There are several treatment options available for GVHD. It is important for a person to work with a doctor to understand the risks of a stem cell transplant, and to monitor for GVHD after the procedure.