According to an article recently published in The New England Journal of Medicine, differences in a gene that controls the production of interleukin-10 (IL-10) appears to help predict the risk of acute graft-versus-host-disease and treatment-related mortality in patients treated with an allogeneic stem cell transplant.
An allogeneic stem cell transplant is the only curative treatment option for several types of cancer. It is a therapeutic approach utilizing high doses of therapy. The high doses of therapy tend to be more effective of killing cancer cells in some types of cancer; however, the doses are also associated with significant side effects. One common and potentially life-threatening side effect of an allogeneic stem cell transplant is the reduction in levels of blood cells. To restore blood cell levels to normal, stem cells from donors are infused into the patient following the high doses of therapy. The donor stem cells may recognize the cancer cells as foreign and mount an attack against them, augmenting anti-cancer effects of this therapeutic approach. However, the donor stem cells may also recognize the patient’s healthy tissues as foreign and mount an immune attack against them, resulting in graft-versus-host disease (GVHD). GVHD may be acute or chronic and is a leading cause of death associated with allogeneic stem cell transplants. Much effort has been focused on reducing the incidence and/or severity of GVHD in patients undergoing an allogeneic stem cell transplant. One way in which physicians try to reduce the risk of GVHD is to “match” human leukocyte antigens (HLA) of a patient with those of a related donor. Human leukocyte antigens are small protein complexes present on most cells in the body. Physicians try to select a donor that has identical (or as close to identical as possible) HLAs to that of the patient in order to reduce the risk of GVHD caused by the donor stem cells.
Researchers from the Fred Hutchinson Cancer Research Center recently evaluating several different genes that were involved in regulating immune responses, such as those thought to be associated with GVHD. This study included over 900 patients who were treated with an allogeneic stem cell transplant from a sibling HLA-matched donor. The researchers discovered that differences in the gene responsible for IL-10, a substance associated with modulating immune responses, significantly affected the risk of acute GVHD following the transplant and death associated with the transplant. Patients with a specific variance in the gene, denoted as A/A, had less than a 10% risk of developing acute GVHD, compared to other variances that had a greater than 20% risk of developing acute GVHD. In addition, patients with A/A had a 12% risk of treatment-related mortality, compared to a nearly 30% risk of treatment-related mortality associated with other variances. Researchers believe that the reduced risk of acute GVHD and treatment-related mortality is due to the high production of IL-10 caused by the genetic variance, which suppresses immune responses, including the immune attack of donor stem cells against patient’s healthy tissues.
The researchers concluded that patients with a genetic variance associated with overproduction of IL-10 appear to be at a significantly reduced risk of developing acute GVHD following an allogeneic stem cell transplant and a reduced risk of treatment-related mortality. This risk assessment may help guide treatment decisions for patients eligible for an allogeneic stem cell transplant, as well as provide further information into the biological mechanisms underlying GVHD. Patients who are to undergo an allogeneic stem cell transplant may wish to discuss the risks and benefits of testing for these genetic variances with their physician.
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Reference: Lin M-T, Storer B, Martin PJ, et al. Relation of an Interleukin-10 Promoter Polymorphism to Graft-versus Host Disease and Survival after Hematopoietic-Cell Transplantation.
The New England Journal of Medicine. 349:2201-2210
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