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Graft versus Host Disease (GvHD)

With allogeneic transplants, a complication known as graft-versus-host disease (GvHD) can develop. GvHD occurs when white blood cells from the donor (the graft) identify cells in the patient’s body (the host) as foreign and attack them. The most commonly damaged organs are the skin, liver, and intestines. This complication can develop within a few weeks of the transplant (acute GvHD) or much later (chronic GvHD). To prevent this complication, the patient may receive medications that suppress the immune system. Additionally, the donated stem cells can be treated to remove the white blood cells that are the primary cause GvHD in a process called “T-cell depletion”.

Acute GvHD Symptoms

Acute GvHD is usually assumed to appear within the first 100 days after transplant. Acute GVHD can range from mild to life-threatening. Symptoms depend on which parts of your body it affects and how severe it is:

It may appear as a rash on the skin. It often starts on the palms of the hands and soles of the feet, and can spread later to other parts of the body. If GVHD is severe, the skin may blister and peel. There may be cramping, nausea or diarrhoea if it affects the stomach or intestines. There may be yellowing of the skin and eyes (jaundice) if the liver is it affected.

Chronic GvHD Symptoms

The most common symptoms of chronic GvHD are:

A rash or changes in skin colour or texture; dry or irritated eyes; pain, dryness or sensitivity in the mouth. Other less common symptoms of chronic GvHD include: Thinning hair; brittleness or changes in the texture of fingernails; dry or irritated vagina; nausea, vomiting, diarrhoea, a loss of hunger or an unexplained drop in weight

Factors Affecting the GvHD

HLA (Human Leukocyte Antigen) disparity between the allogeneic HSCT donor and transplant recipient is the most powerful known factor governing the severity of both acute and chronic GvHD. Sex mismatching and donor parity have been associated with an increased risk of acute GvHD. Another key factor is age of the recipient and donor: GvHD is more frequent and severe in older persons. The source of allogeneic stem cells (marrow vs blood) also may influence the development of GvHD. The incidence of acute GvHD after HLA-identical transplantation varies inversely with the efficacy of post-transplant immunosuppressive prophylaxis.

Conditioning regimens containing total body irradiation (TBI) are associated with higher incidence and severity of GvHD, compared with those involving only chemotherapy. An increased dose of a TBI-conditioning regimen also is associated with an increased risk of acute GvHD.

Incidence of the Disease

Figures for the overall incidence of the disease in both its manifestations are unclear and may not be particularly helpful because the figures arise from a variety of sources and are based on specific starting variables; nevertheless, a number of source* quote approximate figures in the region of 50% of transplant recipients.

Figures from the American Society for Blood and Marrow Transplantation suggests that the acute phase occurs in 9% – 35% of patients and chronic GvHD occurs in 40% – 50%#. The risk of GvHD is believed to rise strongly with age@. Younger than 20 years – 20% risk. 45 – 50 years – 30% risk. Older than 50 years – 80% risk

Mortality

A definitive overall mortality rate is not available or particularly informative. Nevertheless, to obtain a concept of scale, sources quote the following: the American Leukaemia Society gives an overall mortality rate of 30% of all patients who contract GvHD.

Broadly, then with a European figure in 2006 of 10,000 transplants. 50% contracting GvHD (either acute or chronic or both) with 30% of these being lethal would give a very rough figure of 1,500 deaths per annum in Europe.

Current Diagnostic Approach

The main diagnosis comes from early symptoms being confirmed by microscopic analysis of a biopsy (histopathology). Histopathology is the branch of pathology which deals with the tissue diagnosis of disease.

One of the difficulties of diagnosing GvHD and viral infection can be histologically similar. One of the primary objectives of the project is to contribute to the development of a prognostic index able to give guidance on the likely outcome of a stem cell transplant; one of the key challenges of the project is to see whether the analytical approaches identified as an early diagnostic indicator can differentiate between GvHD and infection.

  # Blood and Marrow Transplantation Reviews published by American Society for Blood and Marrow Transplantation

 @  Figures taken from “ Essential Pediatric Allergy, Asthma, and Immunology” p.161-162  By R. L. Wolf, McGraw Hill 2004

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