Specific Changes in Immune System Components Predict Likelihood of Fungal Infection in Allogeneic Stem Cell Transplants

Posted on October 27th, 2008 by

Specific Changes in Immune System Components Predict Likelihood of Fungal Infection in Allogeneic Stem Cell Transplants

Changes in specific immune system components referred to as toll-like receptors (TLRs) predict the likelihood of patients becoming infected with the serious fungal infection, aspergillosis.

Treatment with stem cell transplants is used in several different types of cancers. A stem cell transplant involves the use of high doses of chemotherapy and/or high doses of radiation therapy in an attempt to kill more cancer cells than standard doses. Unfortunately, the high doses of therapy are also responsible for more severe side effects, including low levels of blood cells. Because the side effects associated with a stem cell transplant can be life-threatening, preventing or reducing them is essential.

Blood is composed of three main types of blood cells: red blood cells, which help carry oxygen and nutrients to cells throughout the body; white blood cells, which help to fight infection; and platelets, which help the blood to clot when appropriate. Hematopoietic stem cells, which can be collected from circulating blood or bone marrow, are immature blood cells that can mature into one of the three main types of blood cells. A stem cell transplant involves the collection of stem cells prior to high-dose therapy, followed by re-infusion of these stem cells following therapy. Re-infusion is aimed at restoring blood cell levels to normal and reducing the life-threatening effects of low blood cell levels.

Stem cell transplants may be autologous or allogeneic. An autologous stem cell transplant involves the collection of stem cells from the patient prior to therapy. The stem cells are frozen and re-infused following therapy. An allogeneic stem cell transplant involves the collection of stem cells from a donor; donor stem cells are infused into the patient following therapy.

There is a high risk for infection following a stem cell transplant, as the high doses of therapy often severely reduce white cell levels and weaken a patient?s immune system. Minor infections can often turn into life-threatening situations. Researchers continue to evaluate ways to prevent such infection; preventive approaches include using agents that stimulate immune cells production. Fungal infections such as aspergillosis pose serious and potentially life-threatening risks for patients, as it becomes difficult to treat once it is established. Thus, the prevention of these types of infections is an important issue that continues to undergo extensive research.

Researchers from Seattle recently conducted a clinical study to evaluate differences in donor cells and potential associations in the rate of developing aspergillosis among patients undergoing an allogeneic stem cell transplant. The researchers evaluated differences, or polymorphisms, in different genes for the toll-like receptors among donors and associated outcomes among patients in regards to the incidence of aspergillosis. The study included 336 patients who had undergone an allogeneic stem cell transplant.

The researchers found that if a patient’s unrelated donor had TLR4 haplotypes (S3 and S4), the patient had a significantly increased risk of developing aspergillosis following the transplant (this association did not exist among patients whose donors were related.)

At three years following a transplant, patients had a significantly increased risk of becoming infected with aspergillosis if either the donor or patient was infected with cytomegalovirus (CMV).

The researchers concluded that patients undergoing an allogeneic stem cell transplant had a significantly?increased risk of developing aspergillosis if donor cells they received had specific alterations referred to as TLR4 haplotype S4. As well, infection with CMV among donors or patients was also associated with an increased risk for patients undergoing a transplant to become infected with aspergillosis.

Patients who are to undergo an allogeneic stem cell transplant may wish to speak with their physician regarding their individual risks and benefits of testing for TLRs or the participation in a clinical trial further evaluating markers that may be associated with differences in outcomes. Two sources of ongoing clinical trials include the National Cancer Institute (cancer.gov) and eCancerTrials.com.

Reference: Bochud P-Y, Chien J, Marr K, et al. Toll-like Receptor 4 Polymorphisms and Aspergillosis in Stem-Cell Transplantation. New England Journal of Medicine. 2008;359:1766-1777.

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Tags: Allogeneic Stem Cell Transplant

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