Graft-versus-host disease

When the transplant attacks the donor’s cells

Two types of immune response are possible in the case of an allogeneic transplant: rejection and the graft-versus-host (GVH) reaction.

Graft-versus-host disease occurs when certain kinds of white blood cells, the lymphocytes, contained within the transplant attack the recipient’s tissues, which the former perceive as being foreign. In a phenomenon that is the inverse of rejection, the recipient’s body, which is in a state of immune deficiency, cannot respond to such an attack.

Acute graft-versus-host disease is seen in around 30% to 50% of allogeneic transplants among immediate family members and in 50% to 80% of such transplants not involving siblings.

Acute GVH disease

This disease usually occurs with the first 100 days following the transplant. Symptoms include:

skin disorders: redness, itching, scaling
liver damage: jaundice, elevated liver enzymes
problems of the digestive tract: nausea, loss of appetite, vomiting, cramps and diarrhea

Chronic GVH disease

It generally occurs after the 100-day period following the transplant. Its onset is indicated to varying degrees by a wide spectrum of symptoms that can differ from one patient to another:

skin disorders: sclerosis (thickening of the skin), hyperpigmentation, hair loss, nail dystrophy
damage to the mucous membrane: ulcers, dryness
digestive tract disorders: dysphagia (difficulty swallowing), malabsorption, pancreatic deficiency, diarrhea
bone marrow disorders: anemia, leukopenia, thrombopenia
liver damage
musculoskeletal problems: pain, cramps, stiffness

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Are lymphocytes good or bad?

One of the roles of lymphocytes is to recognize the presence of dysfunctional cells and foreign organisms in the body and then to go on the attack and eradicate them. They are therefore very useful in, for example, eliminating tumour cells. This is what is known as the “graft-versus-leukemia” (GVL) effect, which is highly desirable when patients’ bodies need to be given the resources to be able to fight disease on their own.

However, lymphocytes can also have a pernicious effect: they may not only attack tumour cells, but also the healthy cells in recipients’ bodies, in what is referred to as the “graft-versus-host” effect. One of the difficulties in this procedure is therefore to trigger the GVL effect while preventing GVH—a real challenge, since the same cells, the lymphocytes, are at the source of both effects.