Last year, as he raced his bicycle through lonely farm country roads in the heart of the American Midwest, Christian Beattie couldn’t get enough air.
Here’s a guy who forged lungs of steel through thousands of miles of training—a fierce rider who competed on the open roads and cyclocross trails—and he couldn’t get enough air. He didn’t know it then, but he also didn’t have enough platelets, which help the blood clot. Alone on a training ride, he was one spill away from disaster.
When his gums started bleeding as he brushed his teeth, Beattie knew something was very wrong. The culprit that had started tearing his body apart was acute myelogenous leukemia, and it came with a grim prognosis: a 20 percent chance of being alive in two years.
The way of besting these odds rested on a bone marrow transplant, a Nobel Prize-winning treatment developed at Fred Hutchinson Cancer Research Center.
But Beattie could not find a donor with enough shared biological characteristics to make a transplant viable—not a single match among the 20 million people registered as donors worldwide.
Dr. Colleen Delaney
“The doctors were saying I had better odds of getting hit by two meteorites in a day than finding a donor,” Beattie said.
As he searched for answers, a friend sent him an article about Fred Hutch’s Dr. Colleen Delaney, whose pioneering work harnessing lifesaving cells from
umbilical cord blood was making national and international headlines.
Her efforts were a ray of hope to Beattie, one of the nearly 40 percent of blood cancer patients who need a transplant—16,000 annually—but can’t find a match. For most ethnic minorities, the chance of finding a donor is even lower.
“The Hutch invented transplantation,” he learned after reading his friend’s article. “Why wouldn’t I go there for a transplant?” And so, he did.
Not too long ago, seeking a suitable donor for a transplant patient was like looking for the proverbial needle in a haystack. But today, thanks to the relentless inventiveness of investigators and physicians—with the bulk of groundbreaking research contributions coming from Fred Hutch and its treatment arm, Seattle Cancer Care Alliance—there are plenty more needles in that haystack, so many that we’re coming closer than ever to reaching the long-sought goal of being able to offer a transplant for every patient in need.
“We can do transplants for just about everybody, and we have several ways of getting there,” said Dr. Paul Martin, director of Fred Hutch’s Long-Term Follow-Up Program, which monitors the health of several thousand transplant patients who have undergone the procedure here in the past four decades.
“But blood or marrow transplantation is a very complicated procedure, and every situation is unique,” he said. “That’s why everyone at the Hutch and SCCA is dedicated to making transplantation safer and more widely available to those who need it.”
To understand how far we have come with transplantation, it’s important to remember that once there were no successful treatments for leukemia and other blood cancers. A diagnosis almost always had one single outcome: death.
Dr. E. Donnall Thomas changed that dire outlook. With his colleagues at Fred Hutch, Thomas pioneered a treatment using a mixture of chemotherapy, radiation and a bone marrow transplant from a related donor to treat patients with advanced leukemia.
As Thomas and his team refined the procedure through the mid-1970s, it became possible to offer transplantation to about 30 percent of all patients who were lucky enough to have a suitable match in a sibling. However, that still left a whopping 70 percent of patients with no chance to have a transplant.
In 1979, the Hutchinson Center overcame another major barrier by completing the first successful transplant with marrow from an unrelated donor. The transplant offered hope to another 30 percent of blood cancer patients who had no matching siblings.
Fred Hutch also established the first non-related donor program—a list of about 200 people that included Center employees. From its modest beginnings, Fred Hutch’s program eventually developed into national and international bone marrow registries, which now combine for about 20 million people who have signed up as potential donors.
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.
Two more ways around the problem
Transplantation is indeed saving many more lives today, but Dr. Fred Appelbaum, director of Fred Hutch’s Clinical Research Division, said it’s important to remember that more than 50,000 patients will die of leukemia or lymphoma in the United States this year without the benefit of transplantation.
“In many cases, this is because no donor is available. We need to continue to pursue the goal of finding a safe donor for every patient in need,” he said.
As the search for donors goes on, investigators have focused on two additional sources of donor cells available to patients: haploidentical (half-matched) family members or unrelated cord blood.
A haploidentical donor shares half of the human leukocyte antigen (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.
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 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, O’Donnell 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. Cord blood is harvested from the umbilical cord and placenta and stored for future use. 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 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, it has historically taken more time to restore blood counts after cord blood transplantation than with marrow or adult blood cells.
The ‘ultimate recycled product’
When Beattie heard about Delaney’s work at Fred Hutch, he did his homework and discovered she was one of a handful of investigators in the world conducting extensive cord blood research for treating blood cancers.
“I had to go see her, I had to go to Seattle,” he said.
Delaney developed a technique that expands the number of cells in a cord blood product 200-fold. And she is working on increasing that number to treat adults more effectively. No other researcher has come close to matching her results.
“It really is the ultimate recycled product,” Delaney said. “You can give life to a child and by reusing what is normally thrown away, save the life of someone else.”
Because the cells found in cord blood are less developed than adult stem cells, they don’t need to be as closely matched to a patient, allowing a match to be found for nearly all patients.
Cord blood has other advantages as a stem cell source: It 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.
Beattie received an expanded cord blood transplant and left the hospital in just 10 days, with the underpinnings of a healthy immune system—far faster than with a traditional transplant and with few side effects.
Now, Delaney and colleagues are taking their work further, developing an approach to cord blood transplants that doesn’t require patient-donor matching.
Under this new study, she is working to develop expanded, “off-the-shelf” cord blood units that can be frozen and made available to all patients.
“I want people to know everyone has a match,” said Beattie, whose plans now include cycling into his 40s and beyond.
A bright future for transplantation
Dr. Ann Woolfrey, who directs the unrelated donor program at Fred Hutch, 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,” she said.
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 healthy lives after a transplant, no matter where they live.”