Unrelated, matched donors appear to be just as effective as related, matched donors for children with acute lymphocytic leukemia receiving an allogeneic bone marrow transplantation, according to a recent article published in the Journal of Clinical Oncology.
Acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, is a cancer of the bone marrow and lymph system. The bone marrow produces early blood-forming cells, called stem cells, which grow and mature into the three blood cell types: white blood cells, which fight infection; red blood cells, which carry oxygen to the tissues; and platelets, which help the blood to clot. ALL is characterized by uncontrolled production of immature lymphocytes, or white blood cells. These immature lymphocytes never mature enough to perform their specific function of fighting infection. In addition, these rapidly dividing cells crowd out and suppress the formation of other important blood cells such as the red blood cells, platelets and other white blood cells. ALL is an aggressive cancer and must be treated aggressively in order to achieve optimal chances for a cure.
Patients with acute leukemias or lymphomas are often treated with high doses of chemotherapy and/or radiation followed by a stem cell transplant. Although high-doses of therapy are more effective at killing cancer cells, the treatment procedure also destroys many other cells in the body, including stem cells. A bone marrow or stem cell transplant is a procedure that replaces the stem cells that are destroyed by high-dose chemotherapy and/or radiation therapy with healthy stem cells. In the case of an allogeneic transplant, stem cells are collected from the blood or bone marrow of a related or unrelated donor and infused into the patient after high-dose chemotherapy or chemotherapy plus total body irradiation. In allogeneic transplant further supplements the high-dose therapy by inducing a graft-versus-leukemia effect, through which the foreign donor stem cells (ie, the graft) attack the remaining cancer cells. However, the donor lymphocytes may also attack the patient’s healthy tissues, causing what is called graft-versus-host disease (GVHD). GVHD can be an acute or chronic disease and occurs in the majority of patients receiving allogeneic transplants.
In an effort to prevent or reduce GVHD, attempts are made to match 6 different proteins (HLA) found on stem cells between donors and patients. Often, patients have a “matched” sibling or family member who is able to donate stem cells. However, many patients that could be cured with an allogeneic stem cell transplant do not have a “matched” family member and must rely on an unrelated donor.
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Recently, researchers in Europe compared outcomes of children with ALL receiving a transplant with either matched sibling donors or matched unrelated donors. Patients being evaluated received their transplant between 1990 and 1997 in one of 7 Nordic cancer centers. All patients were in second remission when receiving their transplant. The 5-year survival rate was 39% for sibling donor transplants versus 54% for unrelated donor transplants. The estimated overall post-transplantation cancer recurrence rate was 76% for patients with sibling donors, compared with 40% for patients with unrelated donors. Treatment-related death occurred in 19% of patients with sibling donors and 11% of patients with unrelated donors. The incidence of severe, acute GVHD was 14% in patients with sibling donors, compared with 32% in patients with unrelated donors. Chronic, extensive GVHD incidence was 13% in patients with sibling donors, compared with 22% in patients with unrelated donors.
These results indicate that unrelated, matched donors appear to be just as effective as related, matched donors for children with ALL. Unrelated donors were not associated with a higher treatment mortality although acute and chronic GVHD were more frequently demonstrated. These results are encouraging for patients who may achieve a cure with an allogeneic transplant but do not have a matched related donor for the procedure. Patients who have been advised to receive treatment with a stem cell transplant but do not have a related donor may wish to speak with their physician about the risks and benefits of undergoing this procedure with a matched, unrelated donor. (Journal of Clinical Oncology, Vol 19, Issue 14, pp 3406-3414, 2001)
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