According to results from two studies recently published in The New England Journal of Medicine, hematopoietic stem cells from the umbilical cords of newborn infants provide an effective alternative to hematopoietic stem cells from the bone marrow of donors for an allogeneic stem cell transplant in patients with leukemia who cannot find a matched 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 donor’s hematopoietic stem cells following treatment. The donor’s 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. Trials are ongoing to determine the role of cord blood in allogeneic stem cell transplants.
The first study published in The New England Journal of Medicine included data obtained from the analyzed data from the International Bone Marrow Transplant Registry and the National Cord Blood Program. The data included patients with leukemia who underwent an allogeneic stem cell transplant with either umbilical cord hematopoietic stem cells that had one (34 patients) or two mismatched proteins (116 patients), bone marrow hematopoietic stem cells with one mismatched protein (83 patients), or bone marrow stem cells that were a perfect match (367 patients). In this trial, patients who received cord blood tended to have more advanced disease and were a younger age than patients who received bone marrow. Overall mortality, treatment-related mortality and treatment failure rates were all superior among patients who were treated with matched bone marrow; however, these rates were similar among patients who were treated with mismatched cord blood or mismatched bone marrow. Treatment-related mortality was lowest among the patients who had matched bone marrow cells. At 3 years following treatment, cancer-free survival rates were 33% for patients who received matched bone marrow, 23% for patients who received cord blood, and 19% for patients who received mismatched marrow. Similarly, 3-year overall survival rates were highest for patients receiving matched bone marrow hematopoietic stem cells: 35% for those who received matched bone marrow cells, 26% for those who received cord blood, and 20% for those who received mismatched bone marrow cells. The rates of acute GVHD were similar among patients who received matched bone marrow and cord blood, while patients who received mismatched bone marrow had higher rates of GVHD. Chronic GVHD occurred more frequently among patients who received cord blood.
The second study published in the New England Journal of Medicine also compared results from patients with aggressive leukemia who received an allogeneic stem cell transplant with either cord blood (98 patients) or donor bone marrow (584 patients). The data was reviewed from the Eurocord and the European Blood and Marrow Transplant Group in patients who received transplants between 1998 through 2002. All patients who received bone marrow had a perfect donor match, while only 6% of patients who received cord blood had a perfect match. Patients who received cord blood tended to have more advanced disease than those who received bone marrow. At 2 years, transplant-related mortality was 23% for both groups of patients. At 2 years, overall survival was 42% for those treated with bone marrow and 36% for those treated with cord blood. Cancer-free survival at 2 years was 38% for patients who received bone marrow and 33% for those who received cord blood. Upon analysis of several variables, there was no difference in survival between patients who received bone marrow or cord blood when patients were matched for the type of leukemia and stage of disease. Acute GVHD occurred in 26% of patients who received cord blood and 39% of patients who received bone marrow. Chronic GVHD occurred in 30% of patients who received cord blood and 46% of patients who received bone marrow.
The researchers from both studies concluded that cord blood represents a feasible option for a hematopoietic stem cell source in patients with aggressive leukemia undergoing an allogeneic stem cell transplant who are not able to find a matched donor. Patients who might benefit from an allogeneic stem cell transplant, but cannot find a matched donor may wish to speak with their physician about the risks and benefits of a transplant with the use of cord blood, or the participation in a clinical trial further evaluating transplants with cord blood. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (cancer.gov) and www.cancerconsultants.com. Personalized clinical trial searches are also performed on behalf of patients at cancerconsultants.com.
 Laughlin M, Eapen M, Rubinstein P, et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. New England Journal of Medicine . 2004; 351:2265-2275.
 Rocha V, Labopin M, Sanz G, et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. New England Journal of Medicine . 2004; 351:2276-2285.
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