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Umbilical Cord Transplants are Effective in Adults with Leukemia

According to results recently presented at the 31st annual meeting of the European Group for Blood and Marrow Transplantation, umbilical cord blood transplants are effective treatment for adults with leukemia who lack an acceptable stem cell donor.

Leukemia is a type of cancer that originates in and affects the bone marrow and lymph system. The bone marrow produces early blood-forming cells, which are a type of stem cell called hematopoietic stem cells. Hematopoietic stem cells grow and mature into the three blood cell types: white blood cells, which fight infection; red blood cells, which carry oxygen to tissue; and platelets, which help blood to clot. Leukemia is characterized by uncontrolled production of immature lymphocytes (white blood cells), of which there are two types: B and T 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 red blood cells, platelets and other white blood cells. There are several different forms of leukemia, dependent upon which type of cell is affected, the type of genetic mutations in the cancer, and the aggressiveness of the cancer.

Stem cell transplantation is the only curative treatment option for some types of aggressive leukemias. Stem cell transplantation includes the use of high doses of chemotherapy and/or radiation. The higher doses of treatment tend to kill more cancer cells than moderate doses of treatment; however, the high-dose treatment regimens also tend to kill more healthy cells in the body, such as blood cells, leading to increased rates of severe side effects. Following the high doses of treatment, patients receive infusions of hematopoeitic stem cells, or immature blood cells that mature in the body, to replace the blood cells that are killed during treatment.

In an allogeneic stem cell transplant, patients receive a donors hematopoietic stem cells following treatment. The donors cells must be matched to the patients, meaning that sequences of 6 specific proteins (HLA) found on the outside of the cells must be similar to that of the patients. If all HLA match between the donor and patient, it is referred to as a perfect match. Unfortunately, many patients in need of an allogeneic stem cell transplant cannot find a matched donor and are therefore denied treatment. Donor hematopoietic stem cells provide an added anti-cancer attack in that they attack the patients cancer cells. However, they also may attack the patients healthy tissues, resulting in a condition referred to as chronic or acute graft-versus-host disease (GVHD), which can lead to debilitating consequences.

Hematopoietic stem cells can be found in the bone marrow (spongy material inside large bones), circulating blood and the umbilical cord of infants at birth. Unfortunately, the rich source of stem cells within the umbilical cord is discarded in thousands of births that occur daily. Researchers have been evaluating the use of umbilical cord stem cells for the treatment of allogeneic stem cell transplants, in the hopes of utilizing them for patients who cannot find a donor match. Previous trials have indicated their effectiveness in transplants, as well as a reduction in GVHD with the use of mismatched hematopoietic stem cells. One issue with the utilization of cord blood for transplants in adults was that cord blood did not contain enough of the cells necessary for the procedure. However, there are ways to expand the number of necessary cells through laboratory methods, and it has been demonstrated that two transplants with cord blood may improve outcomes compared to one transplant with cord blood. Trials are ongoing to determine the role of cord blood in allogeneic stem cell transplants.

Researchers affiliated with the Eurocord-Netcord Transplant Group recently analyzed data from studies including umbilical cord blood transplants in adults. The data included 171 adult patients who were primarily diagnosed with leukemia. These patients did not have acceptable donors for allogeneic stem cell transplants and underwent transplants with umbilical cord blood after 1997. Nearly 20% of patients had cancer progression following an autologous stem cell transplant. Following the cord blood transplant, cancer-free survival at 2 years was 41% in patients with early-stage disease, 34% in patients with intermediate-stage disease, and 18% in patients with advanced disease at the time of transplant. Acute GVHD occurred in approximately 32% of patients, and at 2 years, the incidence of chronic GVHD was 36%. Death related to the transplant procedure was 51%.

The researchers concluded that umbilical cord blood transplants are an acceptable alternative for stem cell transplantation in patients who are to undergo an allogeneic stem cell transplant, but do not have an acceptable donor. These results indicate that umbilical cord blood transplants may be more effective in earlier-stage disease. Patients with leukemia who do not have an acceptable donor for allogeneic stem cell transplantation may wish to speak with their physician regarding the risks and benefits of umbilical cord transplants.

Reference: Arcese W, Rocha M, Labopin M, et al. Unrelated cord blood transplant in adults with haematologic malignancies. Bone Marrow Transplantation 2005;55 (supplement 2):S88, abstract number O413.

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