Graft versus host disease

Graft versus host disease (GvHD), is a side effect that can occur after an allogeneic transplant.

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What is graft versus host disease (GvHD)?

Graft versus host disease (GvHD) is a common complication of an allogeneic stem cell transplant. It happens when the T-cells of the new immune system, recognise the recipient’s cells as foreign, and attack them. This causes a war between the ‘graft’ and the ‘host’.

It is called graft versus host, because the ‘graft’ is the donated immune system, and the ‘host’ is the patient receiving the donated cells.

GvHD is a complication that can only occur in allogeneic transplants. An allogenic transplant involves stem cells that are donated for the patient to receive.

When a person has a transplant where they receive their own stem cells, this is called an autologous transplant. GvHD is not a complication that can occur in people who are receiving a re-infusion of their own cells.

The doctor will assess patients for GvHD regularly as a part of the follow up care after an allogeneic transplants. For each part of the body affected by chronic GvHD, a score between 0 (no impact) and 3 (severe impact) is given. The score is based on the impact the symptoms have on daily life and this helps the doctors to decide on the best treatment for the patient.

Types of graft versus host disease (GvHD)

GvHD is classed as ‘acute’ or ‘chronic’ depending on when the patient experiences it and the signs and symptoms of GvHD.

Acute graft versus host disease

  • Starts within the first 100 days post-transplant
  • More than 50% of patients who have an allogenic transplant, experience this
  • Most often occurs about 2 to 3 weeks post the transplant. This 2 – 3 week mark is when the new stem cells begin to take over the function of the immune system and make new blood cells.
  • Acute GvHD can occur outside of the 100 days, this is generally only the case in patients who have had a reduced-intensity conditioning regime before the transplant.
  • In acute GvHD, the graft is rejecting its host, not the host rejecting the graft. While this principle is the same in both acute and chronic GvHD, the features of acute GvHD are different from those of chronic.

The severity of acute GvHD is graded from stage I (very mild) to stage IV (severe), this grading system helps the doctors to decide on treatment. The most common sites of acute GvHD are:

  • Gastrointestinal tract: causing diarrhoea which can be both watery or bloody. Nausea and vomiting coupled with stomach pain, weight loss and decreased appetite.

  • Skin: resulting in a rash that is sore and itchy. It often begins in the hands, feet, ears and chest but can spread over the whole body.

  • Liver: causing jaundice which is a build-up of ‘bilirubin’ (a substance involved in normal liver function) that turns the white of the eyes yellow and the skin yellow.

The treating team should assess the patient for GvHD regularly as a part of the follow up care.

Chronic graft versus host disease

  • Chronic GvHD occurs more than 100 days after a transplant.
  • While it can occur at any point post-transplant, it is most commonly seen within the first year.
  • Patients who have had acute GvHD are at a higher risk of developing chronic GvHD.
  • Roughly 50% of patients who get acute GvHD will go on to experience chronic GvHD.
  • It can impact anyone post a stem cell transplant.

Chronic GvHD most often affects:

  • Mouth: causes a dry and sore mouth
  • Skin: skin rash, skin becomes flaky and itchy, tightening of the skin and changes to its colour and tone
  • Gastrointestinal: indigestion, diarrhoea, nausea, vomiting and unexplained weight loss
  • Liver: often presenting with symptoms resembling viral hepatitis

Chronic GvHD can also affect other areas, such as eyes, joints, lungs and genitals.

Signs and symptoms of graft versus host disease (GvHD)

  • Rash, including burning and redness of the skin. This rash often presents on the palms of the hand and soles of the feet. Can involve the trunk and other extremities.
  • Nausea, vomiting, diarrhoea, abdominal cramping and loss of appetite can be sings of gastrointestinal GvHD.
  • Yellowing of the skin and eyes (this is called jaundice) can be a sign of GvHD of the liver. Liver dysfunction can also be seen on some blood tests.
  • Mouth:
    • Dry mouth
    • Increased oral sensitivity (hot, cold, fizz, spicy foods etc.)
    • Difficulty eating
    • Gum disease and tooth decay
  • Skin:
    • Rash
    • Dry, tight, itchy skin
    • Thickening and tightening of the skin which may result in restrictions of movement
    • Skin colour changed
    • Intolerance to temperature changes, due to damaged sweat glands
  • Nails:
    • Changes in nail texture
    • Hard, brittle nails
    • Nail loss
  • Gastrointestinal tract:
    • Loss of appetite
    • Unexplained weight loss
    • Vomiting
    • Diarrhoea
    • Abdominal cramping
  • Lungs:
    • Shortness of breath
    • Coughing that does not go away
    • Wheezing
  • Liver:
    • Abdominal swelling
    • Yellow discolouration of the skin/eyes (jaundice)
    • Liver function abnormalities
  • Muscle and joints:
    • Muscle weakness and cramping
    • Joint stiffness, tightness and difficulty extending
  • Genitalia:
    • Female:
      • Vagina dryness, itching and pain
      • Vaginal ulcerations and scarring
      • Narrowing of the vagina
      • Difficult/painful intercourse
    • Male:
      • Narrowing and scarring of urethra
      • Itching and scarring on scrotum and penis
      • Irritation of penis

Treatment for graft versus host disease (GvHD)

  • Increasing immunosuppression
  • Administration of corticosteroids such as Prednisolone and Dexamethasone
  • For some low grade skin GvHD, topical steroid cream might be used

For the treatment of GvHD that does not respond to corticosteroids:

  • Ibrutinib
  • Ruxolitinib
  • Mycophenolate mofetil
  • Sirolimus
  • Tacrolimus and Cyclosporin
  • Monoclonal antibodies
  • Antithymocyte Globulin (ATG)

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