The challenge of transplantation: suitable matches

Long-Term Follow-Up

The challenge of transplantation: suitable matches

Not too long ago, seeking a suitable donor for a blood or marrow transplant patient was like looking for the proverbial needle in a haystack.

But today, thanks to the relentless inventiveness of researchers and physicians, there are plenty of needles in that haystack, so many that it’s possible to find a suitable match for nearly all patients in need of a transplant.

"We can do transplants for just about everybody, and we have several ways of getting there," LTFU Director Dr. Paul Martin said. "But blood or marrow transplantation is a very complicated problem, and every situation is unique.

"That’s why everyone at the Hutchinson Center and its treatment arm, Seattle Cancer Care Alliance, is dedicated to making transplantation safer and more widely available to those who need it."

At one point, only 30 percent of those who needed a transplant could find a suitable match in a sibling. That left a whopping 70 percent with no chance to have a transplant.

Learn more about how cord blood transplantation is a solution for patients without matching donors:

Cord Blood Transplantation

But over time, advances in the field allowed another 30 percent to find a suitable match in unrelated donors.

Such a feat has its roots at the Hutchinson Center, the first place to have a non-related donor program—a list of about 200 people that included Center employees.

That embryonic program eventually developed into the National Bone Marrow Program, which now has about 15 million potential donors in the registry.

Yet, despite sibling matching and a registry for non-related donors, about 40 percent of people needing a transplant still had no matches at all. 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 to patients: from haploidentical (half-matched) family members or from unrelated cord blood.

A haploidentical donor shares half of the HLA tissue type DNA of the patient. For example, a child receives half of their HLA tissue type DNA from each parent—making each parent a haploidentical match to their child.

It’s not a perfect match like a sibling who happens to inherit from each parent the same combination of HLA tissue type DNA as the patient, but it is suitable for transplantation under certain circumstances.

Cord blood is harvested from the umbilical cord and placenta after a child is born and stored for future use. Dr. Paul O’Donnell, a Hutchinson Center researcher and medical director of the Adult Transplant Service at SCCA, said these procedures have vastly increased our resources to identify suitable donors for patients in need of a transplant.

His area of expertise is haploidentical transplants, which relies on advances in the drug therapies used to prevent graft-vs.-host disease (GVHD). GVHD results when an incomplete match between the donor and patient causes the donor immune system to attack the patient’s tissues. 

One such drug is cyclophosphamide, which is administered on days three and four after the transplant, and then beginning the use of standard immunosuppressive treatments on day five.

"The cost of cyclophosphamide is only about $300—a wonderfully low-tech approach in our high-tech era," he said.

The low-tech approach has been accompanied by lots of high-tech tools as well, he said.

"Over the last 15 years, we have seen so much improvement in treatment and care, in every area. You look at GVHD, toxicity and infections and there are tremendous improvements, tremendous advancements."

The use of cord blood is one of these advances. Once used only in pediatric patients, it’s now possible to combine two different cord blood donations to treat adult patients. But the procedure still has its limitations.

There aren’t enough cord blood banks around the world and it’s a vastly more expensive procedure.

Each cord blood unit has a very limited number of stem cells. For this reason, the time it takes to restore blood counts after cord blood transplantation is longer than with marrow or adult blood cells.

That’s why the Hutchinson Center’s Dr. Colleen Delaney developed a technique that expands the number of cells in a cord blood product 150-fold. And she is working on increasing that number to treat adults more effectively.

Cord blood has advantages as a stem cell source. Cord blood is readily available, fewer viral infections are transmitted with cord blood, and extremely close HLA tissue type DNA matching is less important for cord blood than it is for bone marrow transplants.

That makes it especially promising for the 16,000 leukemia patients diagnosed each year who can’t find a matching bone marrow donor—many of whom are of mixed ethnic or racial ancestry.

So far, several hundred patients have had cord blood transplants at Seattle Cancer Care Alliance , the Center’s treatment arm, with very positive results.

Dr. Ann Woolfrey, who directs the unrelated donor program at the Center, said haploidentical and cord blood donors have vastly changed the world of transplantation.

"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."

Still, researchers understand that finding a suitable donor is just the first challenge. They want to know which procedures are most effective, and they are always looking for ways to refine them and find better ways to treat patients.

"Preventing disease relapse after transplantation is one of the biggest problems we face," O’Donnell said.

"Also, I would like to see effective treatments that don’t cost a lot of money, so-called low-tech improvements that allow transplantation to be applied throughout the world.

"That’s what I would like to be able to do—to give patients as many opportunities as possible to lead a healthy life after a transplant no matter where they live."