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John Wagner, pediatrics

Pediatrics professor John Wagner has found that cells from umbilical cords are as effective as bone marrow in the treatment of leukemia in children.

Umbilical cord blood is as good as bone marrow in treating leukemia

Cord blood need be less closely matched, opening the door for racial minorities and other hard-to-match groups

By Deane Morrison

June 8, 2008

In a stunning turn of fortune for leukemia patients, a University-led study has shown that children with the disease did just as well with transplants of umbilical cord blood as with transplanted bone marrow. Better yet, the cord blood didn't have to be matched to the recipient; as long as the degree of mismatch was limited and the number of cord blood cells available was sufficient, patients receiving cord blood had the same five-year leukemia-free survival rates as those who received bone marrow. The work opens the door to providing a ready supply of white blood cells to leukemia patients from ethnic and racial minorities, who now have great difficulty finding a donor because they are underrepresented in volunteer marrow registries worldwide. The work appears in the June 9, 2007 issue of the journal Lancet. "This has tremendous implications," says senior investigator John Wagner, a University professor of pediatrics and director of the division of pediatric hematology/oncology and bone marrow transplantation. "It means we can find donors now for a majority of our patients. In the United States, for African Americans [the capability is about] 20 percent, confined to partially matched donors in the marrow registries." In matching, doctors try to minimize the chance that transplanted bone marrow or white blood cells will attack the tissues of the leukemia patient, a life-threatening condition called graft-versus-host disease. To do so, they examine four proteins, known as HLA antigens, that are found on the outer surfaces of cells and may provoke an immune response. Each person can have up to two variations of each HLA antigen. The "gold standard" for a match is when all eight (two variations on four proteins) are the same in both donor and recipient. In their study, Wagner and his colleagues analyzed data from transplant centers around the country. The researchers compared 503 cord blood recipients with various degrees of mismatching to 282 "gold standard" matched bone marrow recipients, looking for difference in the five-year survival rate. The results were eye-opening.

"For the first time, the timing of transplantation can be dictated by the patient's needs, as opposed to the availability of the matched bone marrow."--John Wagner

In cord blood, "with every increment in mismatch, we found a correspondingly increased anti-leukemia effect. That means the risk of relapse of leukemia became substantially lower with every level of mismatch." Although it seems counterintuitive, such an effect is also known to occur with bone marrow transplants, but the study found it to be even stronger with cord blood. In other words, even with mismatched cord blood, overall five-year survival rates were comparable to the gold standard of bone marrow transplants, says Wagner. In both cases, the rate was about 38 percent. Umbilical cord blood also was associated with a lower risk of graft versus host disease. "This is quite a surprise finding," he says. "It's of particular importance to those patients who can't even find donors in the marrow donor registries." However, says Wagner, increasing levels of mismatch in cord blood transplants were associated with higher risks of death from transplant-related complications, most commonly infection. Higher numbers of cells in cord blood transplants improved survival rates. Throughout the world, there are approximately 11 million volunteer donors ready to donate bone marrow, Wagner says. In contrast, there are about 300,000 units of cord blood banked so far. Even with such a relatively small supply of cord blood, Wagner says, "we can find donors for many of our patients, particularly those of racial minority descent, because we can use more mismatched transplants." Now, it takes an average of two to four months to obtain marrow from adult volunteer donors. In contrast, cord blood units are already sitting in a bank, and can be used once a confirmatory typing for matching purposes is completed, which takes a week or two. It is crucial, says Wagner, to increase the diversity in cord blood banks. This past year, he says, the U.S. government released funds of approximately $100 million for augmenting the size of the cord blood registry. Some issues remain, including the fact that the number of cells in a cord blood unit has a huge effect on how quickly the patient's bone marrow recovers after transplantation, as well as the risk of side effects such as infections. Therefore, Wagner says, not only must more units of cord blood be banked to increase their diversity of the population in the bank, but the number of cells in each unit must also be increased. "What this study suggests is that cord blood need not be considered a second line of therapy any longer," says Wagner. "For the first time, the timing of transplantation can be dictated by the patient's needs, as opposed to the availability of the matched bone marrow."