A Novel Match for Stem Cell Transplants

Van Besien
Photo by David Christopher

Research nurse Paula del Cerro, RN, (left) and Koen van Besien, MD, (center) are making stem cell transplants more accessible for cancer patients without a donor match.

By Kadesha Thomas

When leukemia or lymphoma patients need a stem cell transplant, finding a donor match can be like a poster-sized game of tic-tac-toe. The transplant depends on a genetic match with so many possible combinations that the number of X’s and O’s needed to line up seems endless.

For about 30 percent of patients, a younger relative, usually a sibling, solves the puzzle by donating bone marrow. Those without a related donor turn to the National Marrow Donor Program registry. But for African-American, Latino-American and Asian-American patients, finding a match in the registry often results in a stalemate — the genes between donor and recipient are often not compatible.

A new procedure, introduced at the Medical Center by Koen van Besien, MD, director of stem cell transplant and lymphoma, is helping to make stem cell transplants more accessible for these patients. Three years ago, his team began a clinical trial to see if combining stem cells from half-matched donors with stem cells from umbilical cord blood could produce successful transplants.

“This is the most exciting thing we do right now,” van Besien said. “We’re able to offer transplants to more people who need it.”

Van Besien first heard about the protocol in 2006 at a conference when it was presented by a group from Spain. By January 2007, he had brought it to the Medical Center. Van Besien vividly remembers his first patient, a frail, 26-year-old, African-American man with a case of acute myeloid leukemia so advanced that physicians gave him only one month to live.

After he underwent the new procedure, that patient lived a full year longer than physicians predicted.

The most important determinants of compatibility between the patient and donor are the human lymphocyte antigens (HLA), which decide whether a person’s immune system will accept or reject what it sees as foreign. With an HLA mismatch, the donated stem cells can attack the recipient's normal tissues, causing graft-versus-host disease.

The complexity comes in because there are six different types of HLA. Each type has hundreds of variations with more being discovered each year. Additionally, each person inherits one set of six HLA types from their father and another set from their mother. For a transplant, the maternal and paternal HLA types have to match in both the donor and the patient.

For some minorities, finding a match is even more difficult. There are fewer minority donors and minorities are more likely to have rare HLA types from an interracial genetic makeup, particularly for African-Americans. “Most African-American persons I talk to have a grandparent or some blood relative who was not African-American,” van Besien noted.

This makes finding a perfect HLA match terribly challenging even for siblings and nearly impossible when using the registry. Minorities are “severely underrepresented” on the national donor registry, said Kirsten Lesak-Greenberg, a spokesperson for the National Marrow Donor Program. African-American and Asian-Americans each make up only 7 percent of the registry’s 8 million donors. About 10 percent of available donors are Latino-American.

“We had to try mismatched transplants,” said van Besien, who has been researching stem cell transplants for more than 20 years. “We didn’t have a choice.”

The new transplant protocol begins with one week of high-dose chemotherapy. Then stem cells extracted from the half-HLA matched donor are introduced, followed by stem cells from the donated umbilical cord blood.

The adult stem cells quickly take root, providing somewhat of an interim immune system. They require only 10 to 14 days to produce red and white blood cells and platelets. But the adult stem cells are only temporarily effective against infection, lasting about one to two months, because they are not completely matched. By the time the adult stem cells lose their effectiveness, however, the stem cells from the cord blood start to take over. Within 40 days after the transplant, the cord blood stem cells begin reproducing mature, healthy red blood cells, white blood cells and platelets, developing into a fully functional immune system.

Two years ago, African-Americans and Latino-Americans each represented only 8 percent of the Medical Center’s patients who were eligible for stem cell transplants. That number now has jumped to 25 percent for African-Americans and 12 percent for Latino-Americans. The larger increase in African-American patients reflects the Medical Center’s primary service area, which is largely African-American.

Of the 40 patients who have had this type of transplant, half have passed away. But they lived months, even years, longer than expected. Others are cured and living a normal life. “That’s good,” van Besien said, “because none of them would have been around without this.”