SN7 SHORT NOTE 5M

Describe graft-versus-host disease with its requirements, features and prevention.

Pathology · 2nd Professional — Para-Clinical

Definition

Graft-versus-host disease (GVHD) occurs when immunocompetent donor T lymphocytes recognise and attack the tissues of an immunosuppressed recipient.

The three requirements — Billingham criteria

1. The graft must contain immunocompetent cells
2. The recipient must be immunologically incapable of rejecting them
3. There must be histocompatibility differences between donor and recipient

Settings in Which It Occurs

Allogeneic bone marrow or haemopoietic stem cell transplantation — by far the commonest
Transfusion of non-irradiated cellular blood products to a severely immunosuppressed patient, or to a recipient sharing a haplotype with the donor (a risk in related directed donation)
Solid organ transplantation of lymphoid-rich organs — small bowel, liver
Maternofetal transfusion into an infant with severe combined immunodeficiency

Acute and Chronic Forms

Feature	Acute GVHD	Chronic GVHD
Timing	Within 100 days	After 100 days
Mechanism	Donor CD8 and CD4 T cells; cytokine storm	Fibrosis and autoimmunity; resembles an autoimmune disease
Skin	Maculopapular rash starting on palms, soles and ears; may progress to bullae and desquamation	Lichenoid then sclerodermatous thickening; alopecia
Liver	Cholestatic jaundice; bile duct destruction	Chronic cholestasis, cirrhosis
Gut	Profuse watery or bloody diarrhoea; crypt cell apoptosis with "exploding crypts"	Malabsorption, oesophageal strictures
Other	—	Sicca syndrome (dry eyes and mouth), bronchiolitis obliterans, myositis; resembles systemic sclerosis and Sjogren syndrome

CLINICAL PEARL

The three target organs of acute GVHD are skin, liver and gut — the surfaces with the highest antigen load and the most rapid cell turnover. A rash on the palms and soles with diarrhoea and a rising bilirubin after a marrow transplant is GVHD until proved otherwise, and biopsy of the skin or rectum confirms it.

Prevention and Treatment

HLA matching — the most important measure; a fully matched sibling gives the lowest risk
Prophylactic immunosuppression — ciclosporin or tacrolimus with methotrexate
T cell depletion of the graft reduces GVHD but raises the risk of graft failure, infection and relapse of the leukaemia
Irradiation of cellular blood products for at-risk recipients — the definitive preventive measure for transfusion-associated GVHD, which is otherwise almost always fatal
Treatment — high-dose corticosteroids first-line; second-line agents for steroid-refractory disease

Applied Aspects

Transfusion-associated GVHD carries a mortality above 90%, because the marrow is also attacked, causing aplasia — unlike GVHD after a marrow transplant, where the marrow is of donor origin and is spared
The graft-versus-leukaemia effect means some degree of GVHD is beneficial in leukaemia, reducing relapse — which is why complete suppression is not the aim
Chronic GVHD is the leading cause of late morbidity after allogeneic transplantation, and requires prolonged immunosuppression with its own risks
Infection is the usual cause of death, from the disease and its treatment together
Always specify irradiated blood for patients with Hodgkin lymphoma, after purine analogue therapy, for intrauterine and neonatal exchange transfusion, and for directed donations from relatives

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