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Gene Variant Linked to Graft-Versus-Host-Disease

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The identification of a specific genetic variant is associated with a significantly increased risk of developing graft-versus-host-disease among cancer patients undergoing a stem cell transplant. These results were recently published in the New England Journal of Medicine.

Patients with certain types of cancers, specifically leukemias and lymphomas, can be candidates for undergoing a stem cell transplant.

A stem cell transplant is considered to be an intense treatment with associated risks. The procedure includes initial therapy with chemotherapy and/or radiation to kill as many cancer cells as possible. Unfortunately, this treatment also kills healthy cells, including early blood cells.

Low levels of these blood cells can lead to serious consequences, even death, if they are not restored to normal levels.

Therefore, donor blood-forming stem cells are infused into the cancer patients following treatment in an attempt to restore blood cell levels as quickly as possible.

One potential life-threatening consequence of infusion of donor cells is a condition referred to as graft-versus-host-disease (GVHD). This is caused by the patient’s immune system attacking the donor cells, in addition to attacking healthy cells in the body.

Researchers have been evaluating ways in which to reduce the risk of GVHD, including the identification of factors associated with risks.

Researchers from the Fred Hutchinson Cancer Center recently conducted a clinical trial to identify specific genetic variances among patients and potential associated risks of developing GVHD following a matched-donor stem cell transplant.

The trial included over 1,400 recipients of a stem cell transplant who were tested for specific genetic variants.

The researchers stated that “The risk of GVHD associated with HLA-DPB1 mismatching was influenced by the HLA-DPB1 rs9277534 expression marker. Among recipients of HLA-DPB1–mismatched transplants from donors with the low-expression allele, recipients with the high-expression allele had a high risk of GVHD.”

In essence, these results mean that very specific genetic variances have been identified that are associated with an increased risk of developing GVHD (54% increased risk). Ultimately, these results will help identify optimal matches for donors and recipients of stem cell transplants.

Reference: Petersdorf E, Malkki M, O’hUigin C, et al. High HLA-DP expression and graft-versus-host disease. New England Journal of Medicine. 2015; 373:599-609.