Options for People Without a Match
The Fred Hutchinson Transplant Program at Seattle Cancer Care Alliance (SCCA) provides an opportunity for nearly anyone to receive a bone marrow transplant—even without a matched donor—using haploidentical and cord blood transplants.
“We can do transplants for just about everybody, and we have several ways of getting there,” said Paul J. Martin, MD, director of Long-Term Follow-Up for the Fred Hutchinson Transplant Program at SCCA.
Transplants with Matched Unrelated Donors
At one time, only 30 percent of those who needed a transplant could find a suitable match (based on HLA typing)—because they had a matched sibling available to donate. That left 70 percent with no chance at a transplant at all.
Over time, advances in the field allowed another 30 to 35 percent to find a match among unrelated donors. This option has its roots at Fred Hutchinson Cancer Research Center, the first place to have an unrelated donor program—a list of about 200 people, including Hutch employees, willing to donate to a stranger. That program eventually developed into the National Marrow Donor Program, which now has more than 20 million potential donors in its registry.
Even when patients expand the search outside their family to all registered donors worldwide, it can be difficult to find a match. Until recently, about 35 to 40 percent of people who needed a transplant still had no match. It was a problem in need of a major solution, and researchers went to work.
Today, there are two additional sources of donor cells available: haploidentical (half-matched) family members and cord blood.
An HLA-haploidentical donor shares a haplotype with the transplant recipient. This means that the donor and recipient have the same set of closely linked HLA-genes on one of the two number six chromosomes they inherited from their parents. Rather than being a perfect match for each other, they are a half-match. Parents are always a half-match for their children and vice versa. Siblings have a 50-percent chance of being a half-match for each other. (They have a 25-percent chance of being a perfect match and a 25-percent chance of not matching at all.)
Cord Blood Transplants
Cord blood is collected at the time of a baby’s birth with no risk to the infant or mother. After the umbilical cord is cut, a needle is inserted into the vein of the umbilical cord, and the leftover blood from the placenta and umbilical cord is collected and stored for future use. The blood-forming stem cells from cord blood are more versatile than those from bone marrow or peripheral blood when used for a transplant, simply because the immune cells in cord blood are naïve. They aren’t yet educated against foreign invaders, such as bacteria and viruses. So there’s less likelihood of an adverse interaction between the transplanted cells and the recipient’s tissues. As a result, they don’t need to be such a close match to be transplanted successfully. Importantly, this means that cord blood donors can be identified for almost all patients in need of a transplant, even if the patient cannot identify a matched adult unrelated volunteer donor.
Improving the Odds
Haploidentical and cord blood options have changed the world of transplantation, greatly improving the odds of finding suitable donors for people who need a transplant.
“Today, more than 90 percent of our searches result in a donor. And, yes, we still need all these different procedures. When it comes to the diseases treated with blood and marrow transplantation, there’s no one-size-fits-all approach,” said Ann E. Woolfrey, MD, who directs the unrelated donor program at the Hutch.
The Fred Hutchinson Transplant Program at SCCA provides transplants using cells from the patient and from both related and unrelated donors, including haploidentical transplants and cord blood transplants. Our transplant team has well-developed clinical studies available for people who need any type of transplant.
Better Transplant Outcomes
“Many centers across the country are finding that outcomes of transplants using haploidentical or cord blood donors are very similar to outcomes of transplants using matched donors,” said Paul V. O’Donnell, MD, PhD, a researcher in the Clinical Research Division at the Hutch and previous medical director of the Adult Blood and Marrow Transplant Service at SCCA. “The rates of acute or chronic graft-versus-host disease (GVHD) are surprisingly less than or similar to the rates with matched donors using current protocols.”
GVHD results when an incomplete match between the donor and recipient causes the donor immune system to attack the recipient’s (host’s) tissues.
Preventing GVHD in Haploidentical Transplants
Haploidentical transplants rely on advances in drug therapies to prevent GVHD. One preventive therapy uses a high dose of the chemotherapy drug cyclophosphamide given on days three and four post-transplant, followed by standard immunosuppressive treatments starting on day five. This protocol may seem counterintuitive, said Dr. O’Donnell, because high-dose chemotherapy is typically given earlier in the transplant process, during the conditioning phase (to destroy the malfunctioning cells in the recipient’s body). But doctors have found that giving cyclophosphamide after a haploidentical transplant helps prevent GVHD because cyclophosphamide kills certain donor immune cells (T-cells) that would otherwise cause GVHD.
Combining and Expanding Units of Cord Blood
For cord blood transplants, SCCA doctors now routinely combine two units of cord blood (from different donors) to extend this option to adults. Each unit of cord blood has a very limited number of stem cells. So cord blood transplants were once used only in pediatric patients—who, because of their smaller size, don’t need to receive as many stem cells as adults do. By combining units, we can now treat many adults this way.
Still, it takes longer to restore blood counts after a transplant with cord blood than with marrow or peripheral blood from an adult. That’s why the Hutch’s Colleen Delaney, MD, developed a technique that expands the number of cells in a unit of cord blood 150-fold. She is working on increasing that number to treat adults more effectively. Studies show that expanding one of the two units of cord blood in the lab pre-transplant increases the rate of post-transplant engraftment (when the recipient’s body resumes producing blood cells and develops an immune system again).