Graft Versus Host Disease Causes, Symptoms, Treatment

Woman with sore knee
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Graft versus host disease (GVHD) is a common side effect of allogeneic bone marrow or stem cell transplants. Although the chances of developing GVHD vary, 40% to 80% of transplant recipients get GVHD in some form or the other. GVHD is often mild, but occasionally it can be severe enough to be life-threatening. This article will take you through the basics of this important and potentially distressing side effect of a transplant.

Causes

The marrow or the stem cells that are transplanted into the patient contain blood cells of the donor. One type of blood cell present in the donated blood cells is the T cell (or T lymphocyte.) T cells are aggressive cells in the immune system that seek out invaders such as bacteria and viruses and other foreign cells and attack. The problem with a transplant is that those donor T cells now recognize cells in the recipient as being foreign. Therefore the donor (the graft cells) attack the recipient (the host of the transplant).

Before a transplant is done, donors and transplant recipients are HLA matched to decrease the likelihood of this attack, though unless the match is identical (for example, from an identical twin) there is always some chance of developing GVHD.

Symptoms

The most common symptoms of GVHD depend on whether it is an acute (early) or chronic (late) reaction.

  • Acute GVHD - Acute GVHD occurs within 100 days of the transplant and most often affects the skin (rashes), the intestines, and the liver. People may experience rashes which are most predominant on their hands and soles, and sections of skin may actually slough off. Involvement of the intestines can cause nausea, stomach cramps, and diarrhea, whereas involvement of the liver often results in jaundice, a yellowish discoloration of the skin.
  • Chronic GVHD - Chronic GVHD occurs after 100 days and may be related or unrelated to acute GVHD. It occurs more commonly in people who have had acute reactions. Chronic GVHD often affects multiple regions of the body. In addition to involvement of the skin, intestines, and liver as with acute reactions, chronic GVHD often includes dry eyes or vision changes, pain and stiffness in the joints, skin tightening and thickening along with discoloration, and fatigue, muscle weakness, and chronic pain. Chronic symptoms can have a long term negative impact on both physical well-being and quality of life.

Prevention

GVHD is a condition that can be extremely distressing, and the success or failure of a transplant depend a lot on preventing or minimizing the ill effects of this condition. There are several ways that the chance of GVHD can be reduced. These include careful HLA matching, using drugs to minimize GVHD, and removing T cells from the blood of the donor. For some reason, however, removing T cells can have negative impacts on the success of the transplant in other ways.

Careful management of early symptoms of GVHD can be helpful as well, particularly being careful with sun exposure, as this appears to be a trigger for worsening GVHD.

Treatment

GVHD is not easy to treat. It involves the assessment and modification of drugs that are routinely given for preventing GVHD. It also involves adding new drugs, especially steroids, to stop the damage to the organs of the transplant recipient. Occasionally, when the steroids are not enough to effectively control the condition, other drugs may need to be added.

Recently, ibrutinib, a therapy used to treat various types blood cancers including certain non-Hodgkin lymphoma types, was approved in the United States for treatment of adult patients with chronic GVHD after failure of one or more lines of systemic therapy. The approval was based on data from a study of 42 patients with active cGVHD with inadequate response to corticosteroid-containing therapies who were then treated with ibrutinib.

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Article Sources

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