Matching the need for bone marrow transplants

Travis Arnold is in it to win it. The 17-year-old is a top-rated golfer on Klein High School’s Bearkat Golf Team. Academically, he ranks in the top 2% of his class. And two years ago, he kicked cancer to the curb.

At age 12, Arnold was diagnosed with a bone marrow disorder that evolved into acute myeloid leukemia — a fast-growing cancer of the white blood cells.

Doctors hoped a bone marrow transplant rich with stem cells could save his life. Arnold underwent two transplants at another hospital, using marrow from donors who tested genetically as his perfect match. Both transplants failed.

That’s when his parents sought help at MD Anderson Children’s Cancer Hospital, where doctors decided to try something different. They performed a socalled half-match bone marrow transplant, known medically as a haploidentical transplant, with “haplo” meaning “half.”

While half-match donors aren’t a perfect match, they’re close enough to allow patients to move ahead with a transplant.

To test whether a donor’s bone marrow is a suitable match for a recipient, doctors examine genes in the human leukocyte antigen, or HLA System — the part of the immune system that recognizes self and not self.

In a full match, eight to 10 HLA genes need to match between donor and recipient. In a half match, only half of these HLA genes need to match up.

“Parents are always a half-match for their children, and vice versa,” says Stefan Ciurea, M.D., associate professor of Stem Cell Transplantation. “Siblings have a 50 percent chance of being a half-match for each other.”

In Travis Arnold’s case, his father served as his half-match.

Because the matching between donor and recipient is only half, the donor’s immune system may generate a stronger attack against the recipient’s tissues — a condition known as graft-versus-host disease. Certain therapies given before and after the transplant have been very effective in controlling this reaction.

“With chemotherapy and immunosuppressive treatments, the rates of graft-versus-host disease are surprisingly less than or similar to the rates with matched donors,” Ciurea says.

Life begins with second chances

Similar to haploidentical transplants, cord blood transplants are providing effective new treatment options for cancer patients.

At the time of a baby’s birth, after the umbilical cord is cut, a needle is inserted into the vein of the cord, and the blood in the cord and placenta is collected and frozen until it is needed for a transplant.

This infant blood is rich in new stem cells that haven’t yet been educated against foreign invaders, like bacteria and viruses. So its stem cells are less likely than bone marrow stem cells to attack a recipient’s tissues. As a result, the donor and recipient don’t need to be as closely matched as those in a bone marrow transplant.

“A match in four of six HLA markers in cord blood is usually considered acceptable,” says Elizabeth Shpall, M.D., Ph.D., deputy chair of Stem Cell Transplantation and Cellular Therapy and chair of the Cord Blood Transplant Program at MD Anderson.

Since the first umbilical cord blood transplant performed in France almost 30 years ago, the banking of cord blood has played a significant role in saving lives.

Avoiding delays

With half-matched and cord blood transplants providing new sources of stem cells, patients no longer need to delay transplantation while waiting for a perfect or nearperfect donor match.

“People who need transplants are usually very ill, and rapid access to stem cells can save lives,” Shpall says.

Today, practically all patients find a donor, says Dean Lee, M.D., Ph.D., associate professor of Pediatrics and Arnold’s doctor. “With new sources of stem cells, we no longer have to turn away someone who needs a transplant for lack of a donor.”

A study published in the New England Journal of Medicine in 2014 verified that lack of a donor is no longer a major limitation to transplants. More than 99% of white European-Americans and 95% of African-Americans who need a transplant will have a suitable match, according to the study.

Minority donors needed

This is especially relevant for minorities, who are underrepresented in the National Marrow Donor Program’s Be the Match registry — the nation’s largest bone marrow registry. More than 10 million people who are willing to donate their bone marrow to a stranger have signed up. If patients cannot find a match within their family, they must attempt to find an unrelated donor from the registry.

“Bone marrow donations must be matched to very specific genetic markers that are overwhelmingly more likely to appear in donors of the same ethnicity,” Shpall explains. “Because minorities are under-registered, it’s harder for them to find a non-family donor.”

Minorities make up only 25% of donors in the Be the Match registry, according to Cheekswab, an organization dedicated to increasing minority participation. As a result, minorities have a 66 to 73% chance of finding a matching donor through the registry, compared with Caucasians’ 93% likelihood of finding a match.

“Additionally, some ethnic groups have a more complicated gene pool that makes it difficult to find a match through traditional methods,” Shpall says.

Using half-matched donors now compensates for the lack of donors in Be the Match and other registries, Ciurea adds.

“With half-matched transplants generating improved outcomes that are comparable to full-matched transplants, every patient has a chance,” he says.