According to a recent article published in the journal Blood, the removal of T-cells (immune cells) from a stem cell infusion does not reduce the rate of chronic graft-versus-host-disease in patients with cancer who undergo an unrelated (donor other than family member) allogeneic stem cell transplant. However, it may reduce the risk of serious acute graft-versus-host-disease.
Several types of cancers, particularly hematologic cancers (those that originate in blood cells), are most effectively treated with a stem cell transplant. A stem cell transplant often involves the use of high doses of therapy that tend to kill more cancer cells, but also attack healthy tissues and cells, including hematopoietic stem cells.
Hematopoietic stem cells are immature blood cells produced in the bone marrow that mature into red blood cells (which carry oxygen to tissues), white blood cells (which fight infection), and platelets (which aid in blood clotting). In an allogeneic stem cell transplant, stem cells from a donor are infused into the cancer patient.
An important benefit of an allogeneic stem cell transplant is that donor cells will attack cancer cells (graft-versus-tumor effect). However, the donor cells may also attack healthy cells and tissues, resulting in a condition called graft-versus-host-disease (GVHD). This condition may be acute or chronic and can result in life-threatening complications. Furthermore, GVHD significantly reduces the quality of life for these patients. GVHD is more common among patients who receive stem cells from unrelated donors.
Due to the prevalence of chronic GVHD (cGVHD), researchers continue to evaluate ways to reduce its risk and severity. One method under evaluation is the removal of specific T-cells from donor stem cells. T-cells are a type of immune cell that are thought to be one of the key players in GVHD.
Researchers associated with the National Heart, Lung, and Blood Institute Unrelated Donor Marrow Transplantation Trial recently conducted a trial to further evaluate `T-cell depletion from the donor stem cell sample in patients undergoing allogeneic stem cell transplants from unrelated donors. The objective of this trial was to evaluate the effects of T-cell depletion specifically on the incidence of cGVHD.
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This trial included 404 patients who received either T-cell depleted infusions of donor stem cells plus the agent cyclosporine (which suppresses the immune system) or a standard prevention against GVHD consisting of the chemotherapy agent methotrexate plus cyclosporine.
T-cell depletion did not appear to provide protection against cGVHD:
- Incidence of cGVHD was similar at 2 years between the two groups of patients.
- Survival at 3 years from diagnoses was similar between the two groups of patients.
- Incidence of leukemia relapse was similar between the two groups of patients.
- Incidence of serious infections was similar between the two groups of patients.
- Overall, patients who suffered from GVHD had significantly reduced rates of cancer relapse.
- T-cell depletion did, however, reduce the incidence of severe acute GVHD.
The researchers concluded that T-cell depletion from donor stem cells does not reduce the risk of cGVHD or cancer relapse or improve survival in patients undergoing an allogeneic stem cell transplant from an unrelated donor. However, the incidence of acute GVHD (aGVHD) was reduced in these patients. Future trials evaluating aGVHD and T-cell depletion may be warranted for patients undergoing unrelated allogeneic stem cell transplants. Furthermore, the authors stress that the T-cell depletion method utilized in this trial was not as intense as other current methods; this may affect results.
Reference: Pavletic S, Carter S, Kernan N, et al. Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation. Blood. 2005; 106: 3308-3313.
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