September 8, 2016 • Relapsing Polychondritis
When Crystal Day’s cancer came back, the Seattle architect and designer thought she was out of options.
She’d been through chemotherapy to halt the acute myeloid leukemia first diagnosed in 2011, when she was 25. Three years later, doctors said she needed a stem-cell transplant to attack the relapsed disease and reboot her damaged immune system.
The problem? She couldn’t find a match, someone to donate bone marrow or blood stem cells. Not from her family, and not from any of the nearly 27 million potential donors available through an international registry.
“There was no match in the whole world — not even a bad match,” Day now 30, recalled.
But Day’s doctors at the Fred Hutchinson Cancer Research Center had a different idea, one borne out in anew study published Wednesday in The New England Journal of Medicine. They used blood from umbilical cords, two of them, based on growing evidence that such transplants, which don’t require as strict a match, might be as good as — or better than — other common types of stem-cell transplants for blood-cancer patients.
“We had a gut feeling that things were doing well,” said Dr. Filippo Milano, a cord-blood expert at Fred Hutch and first author on the paper. “Our analysis proved that the choice was the right one.”
In their review of nearly 600 leukemia and blood-disorder patients — including Day — who got any stem-cell transplant at the Seattle center between 2006 and 2014, Milano and his colleagues found the chance of survival was at least as high, or higher, in patients who received cord blood rather than two other types of transplants.
Plus, they found that the risk of relapse was lower overall in those who received cord blood versus bone-marrow or blood-cell transplants that were well-matched or mismatched according to human leukocyte antigentyping. That’s HLA, a group of proteins on cells that can trigger an immune-system response.
The study looked at patients aged 1 to 67 and included 140 cord-blood transplants, 344 HLA-matched adult unrelated donors and 98 HLA-mismatched adult unrelated donors.
The findings were particularly strong in about a third of patients in each group, those with what’s called minimal residual disease — in remission with no symptoms, but with cancer cells that can be detected in their system.
The risk of death was almost three times higher in patients who received HLA-mismatched transplants from unrelated donors than in the cord-blood group. It was about 70 percent higher in the HLA-matched group, too, though that didn’t reach statistical significance, the study said.
At the same time, the risk of relapse was about three times lower in patients with some residual disease who received cord-blood transplants versus the other transplants.
In patients with no detectable disease, like Day, the effects were similar, but not as robust, the study found. There was no evidence that the risk of relapse was greater in the cord-blood group, nor evidence of higher death rates than in the HLA-mismatched group. In the HLA-matched group, the risk of death was lower, but not statistically significant.
Stem-cell transplants, no matter what type, are a go-to treatment for some cancer. High-dose chemotherapy and/or radiation kill the cancer cells, then donor cells are transplanted to repopulate the bone marrow.
The new study underscores what Dr. Colleen Delaney, director of the Fred Hutch cord-blood program, has long maintained: Cord blood safely and effectively expands options for high-risk cancer patients.
Delaney, who was last author on the paper, said she shudders when she hears that blood-cancer patients think bone-marrow drives are their only option. This study should spur doctors to think twice about the best source of stem-cell transplants for their patients.
“Nearly everyone will have a cord-blood match,” she said.
That’s important, for several reasons, the Hutch experts said. Although the best donors for a stem-cell transplant are HLA-identical siblings who can provide bone marrow or blood cells, only about 30 percent of patients will have such a match.
The next best option is an unrelated donor who’s a good match for all the HLA markers, followed by an unrelated donor who matches many, but not all, of the markers.
The trouble is, matches can be tough to find, especially for racial and ethnic minorities, according to the National Marrow Donor Program, a Minneapolis nonprofit. It operates Be the Match, a registry of about 13.5 million people, with access to nearly 27 million donors around the world.
In the U.S., nearly 20,000 stem-cell transplants are performed each year, including 900 to 1,000 cord-blood transplants, federal figures show.
While about 97 percent of white patients are likely to have a match, that figure falls to 34 percent for black patients, 28 percent for Asians and 20 percent for Hispanics, NMDP figures show.
For patients like Day, who is half white and half Hispanic, the chances are even lower. Her sister wasn’t a match and neither was anyone in the entire registry. An experimental cord-blood transplant was her only hope — and even that took time.
“I waited for three months before they said they had a cord-blood match,” she said.
It finally worked because cord-blood transplants are different from the others, experts explained. They don’t have to be as closely matched to the patient and they’re more adaptable to the new host, Milano said.
In addition, approximately 680,000 units of cord blood worldwide are stored in public banks, so they can be used right away.
Those benefits and more were apparent in the Fred Hutch study, said Dr. Juliet Barker, director of the cord-blood-transplant program at Memorial Sloan Kettering Cancer Center in New York, who wasn’t involved in the work but called it “a major contribution to the field.”
“This report supports not only cord blood taking the priority over a mismatched unrelated donor, but the consideration of cord blood as an immediate alternative source of stem cells to matched adult volunteer donor transplants, especially in high-risk patients,” she said in an email.
Barker called for a national, randomized, controlled trial of patients with high-risk leukemia, comparing those who receive matched unrelated donor transplants and those who get cord-blood transplants.
Day admitted she was initially wary of the expanded cord-blood transplant. “At first it was scary because it hadn’t been tried before,” she said.
But within four weeks of receiving two umbilical-cord transplants, the cells “engrafted,” or took hold, and she started making her own blood and platelets. For the rest of her life, there will be evidence of the dominant graft — an American baby boy — in her bodily fluids.
“My spit shows 100 percent Irish male,” she said, laughing.
Two years later, Day is in remission. She has returned to work at the Seattle architecture firm Perkins+Will, where, in a coincidence, part of her job was designing new labs and office spaces in the 1100 Eastlake Ave. building on the Fred Hutch campus.
Her experience as a cancer patient has colored her work as a designer, she said.
“My doctor once said that thousands of people have died to help cure you,” she said. “I would like my design work to help the doctors.”