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Graft-Versus-Host Disease

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Overview

Graft-versus-host disease (GvHD) occurs when T-cells from a donor are introduced into a recipient unable to eliminate them using their immune system, leading to the T-cells responding to the recipient’s antigens and stimulating an immune response. It is an important cause of death in bone marrow and stem cell transplants.

GvHD can be acute or chronic. These are differentiated based on presentation rather than time of onset.

It is different to transplant rejection where the recipient generates an immune response towards the donor tissue. In GvHD, the T-cells in the donor generate an immune response to the recipient.

Aetiology

There are two important classes of human leukocyte antigen (HLA) in GvHD:

  • Class I HLA proteins (A, B, C) – expressed on nearly all cells with a nucleus
  • Class II HLA proteins (DR, DQ, DP) – mainly found on haematopoietic cells

In general, for acute GvHD, the incidence directly relates to the degree of disparity between the donor’s and recipient’s HLA antigens. Transplant donors and recipients are usually matched based on these HLAs.

Risk Factors

  • HLA mismatch
  • Differences in age between the donor and recipient
  • Differences in sex between the donor and recipient
  • Malignancy

Example History

A 20-year-old man has acute abdominal pain and diarrhoea. He has passed 3 motions in the last hour. On examination, he has a maculopapular rash on his neck, palms of his hands, and soles of his feet. He received an allogeneic bone marrow transplant 8 days previously.

Presentation

Acute GvHD

Patients usually have skin involvement first and may have a fever. In the past, acute GvHD was considered to be the diagnosis if symptoms arose within 100 days of transplantation. Features may be:

  • Skin features:
    • Pruritic maculopapular rash on the palms and soles
    • Blistering and ulceration
    • Symptoms similar to toxic epidermal necrolysis may occur
  • Gastrointestinal (GI) features:
    • Diarrhoea is the most common feature
    • Vomiting
    • Abdominal pain
    • Anorexia
  • Hepatobiliary features:

Chronic GvHD

Chronic GvHD historically was considered to be the diagnosis if symptoms arose after 100 days of transplantation. It can arise after acute GvHD or arise spontaneously. The features of GvHD are more mixed, involving the skin, GI tract, liver, lungs, heart, kidneys, and bone marrow. Some features are:

Investigations

All patients

Investigations are usually carried out depending on what the presenting complaint is. They are generally to rule out infection:

  • Full blood count (FBC):
    • Not specific for GvHD but may show anaemia, leukopenia, thrombocytopenia, or eosinophilia
  • Blood culture:
    • To screen for infection
  • Urea and electrolytes (U&Es):
    • May be deranged if the kidneys are involved
  • Urinalysis and culture:
    • May show proteinuria if the kidneys are involved
    • Cultures are negative i.e. infection is ruled out
  • Liver function tests (LFTs):
    • May be deranged if the liver is involved
  • Stool culture:
    • To screen for infection
  • Viral PCR:
    • To screen for infection
  • Biopsy of the affected tissue
    • May help diagnosis if there is uncertainty
    • This should not delay diagnosis

Diagnosis is clinical. A bone marrow biopsy may help but treatment should not be delayed waiting for results.

Management

Overview

  • 1st-line: supportive management through corticosteroids + immunosuppression

Monitoring

  • Treatment is often aggressive and immunosuppressive, so patients must be monitored closely for signs of infection/malignancy which may arise as a result of immunosuppression.

Prognosis

  • Early intervention and management are associated with a better prognosis
  • The survival rate with first-line therapy is around 60% but this drops to as low as 20% for those needing second-line therapies.

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