Umbilical cord blood transplant linked to lower relapse in high-risk leukemia patients

Study compares ‘alternative’ donor source vs. traditional transplantation of blood stem cells from an adult, unrelated donor
Crystal Day
Crystal Day, diagnosed with acute myeloid leukemia at 26, received a cord blood transplant two years ago for recurrent disease and has been cancer-free ever since. Photo by Robert Hood / Fred Hutch News Service

Crystal Day was 26 when she was diagnosed with acute myeloid leukemia. With increasing fatigue and near-daily nose bleeds, Day had looked up her symptoms on WebMD and at first thought she just needed more iron. But it didn’t help.

One day, she could barely walk to the front door of her home in North Carolina. She went to urgent care that day, and a blood test soon revealed the cancer overtaking her blood cells.

Her first chemotherapy treatment put the cancer in remission, but her doctor at the time described her situation somewhat ominously: “One way the doctor explained it to me was that the chemo is just killing the tip of the iceberg of your leukemia cells,” said Day, now 31. “There’s no way to actually tell how deep the leukemia cells are in your marrow.”

After she finished treatment, Day and her fiancé moved to Seattle, where she had grown up, and settled into their new lives. But three and a half years after her diagnosis, the cancer came back.

This time, her oncologist at Seattle Cancer Care Alliance, Fred Hutch’s clinical care partner, told Day her only option for a cure was a stem cell transplant. For those like Day, patients with leukemia and other blood cancers, blood stem cell transplants often offer the best hope of a cure. But even with this lifesaving procedure, some patients can relapse — especially if doctors aren’t able to put the cancer into complete remission prior to transplant.

Lacking a matched donor in her family or the national bone marrow registry, Day received a transplant two years ago using cells from umbilical cord blood, and it worked — she’s been cancer-free ever since.

Now, a new study from researchers at Fred Hutchinson Cancer Research Center published Wednesday in The New England Journal of Medicine describes results from Day and others like her — patients who have received stem cell transplants from cord blood or from unrelated adult donors at Fred Hutch. The researchers reviewed outcomes for 582 patients who’d received stem cell transplants at the Hutch from 2006, when the institute’s Cord Blood Program launched, to 2014. Including Day, 140 of those patients received cord blood transplants.

Benefits beyond being an alternative source of stem cells

The study found that such transplants may have advantages beyond offering an alternative stem cell source for patients without a traditional donor match — they seem to perform better against leukemia and the related bone marrow disorder, myelodysplastic syndrome, in patients at high risk of relapse after transplant.

These patients, who make up about a third of those facing a stem cell transplant, have what is known as “minimal residual disease” — the chemo required before transplant isn’t  completely successful at putting their cancer into remission, and small amounts of the disease remain. Only about a third of patients with detectable cancer in their blood at the time of transplant will still be alive three years later, a 2013 Hutch study found, as compared to nearly three-quarters of those without such residual disease.

“Patients going into transplant with minimal residual disease, they have very dismal outcomes,” said Fred Hutch transplantation researcher Dr. Filippo Milano, lead author of the NEJM paper. But this study showed that such patients who received a cord blood transplant had better outcomes and a lower relapse rate than those who received stem cells from an adult unrelated donor, Milano said.

In fact, the patients in their study with minimal residual disease — about one-third of the 582 patients in the study — who were transplanted with cord blood cells were no more likely to relapse or die than patients without the detectable cancer cells who’d also received a cord blood transplant, the researchers found. Those who’d received a traditional transplant from an unrelated donor were on average more than three times as likely to relapse if they had minimal residual disease than those without detectable cancer cells in their blood, and they were more than twice as likely to die.

For the other two-thirds of the patients, those with no minimal residual disease, cord blood transplants and traditional transplants had very similar outcomes.

The researchers’ retrospective study — a look back at how patients already treated have fared, rather than a prospective study, which follows patients from the beginning of their treatment — was originally planned as a sort of internal review, Milano said. But the patients’ outcomes — especially the improved survival that cord blood transplant may offer for those at high risk of relapse — were so encouraging that the researchers decided to write up their findings to share with their colleagues outside the Hutch.

“The idea at the beginning was just to see where we are with the Cord Blood Program here,” he said. “Then we saw the results were very, very good.”

However, the researchers cautioned that it’s difficult to make black and white comparisons with a retrospective study — to definitively say a cord blood transplant is better than a traditional transplant for any group of patients, you really need a prospective study, Milano said. 

Drs. Filippo Milano and Colleen Delaney
Fred Hutch transplantation researcher Dr. Filippo Milano, lead author of The New England Journal of Medicine paper, and senior author Dr. Colleen Delaney, director of the Cord Blood Program at the Hutch. Photo by Bo Jungmayer / Fred Hutch News Service

A transplant where everyone has a donor

Cord blood transplantation offers one known, big advantage over adult donor transplants for the general population, said Dr. Colleen Delaney, who started Fred Hutch’s Cord Blood Program in 2006 and is senior author on the study: “Everyone has a cord blood donor.”

Because stem cells in the umbilical cord are less developed than adult stem cells, they don’t have to be “matched” as stringently to a patient’s human leukocyte antigen, or HLA, type. HLA genes are part of each person’s unique genetic background that determines the likelihood of rejecting donor stem cells. Doctors typically look for a 10-out-of-10 match of HLA genes between patients and their donors, but, if such a perfect match doesn’t exist among relatives or unrelated donors, they’ll often go with an eight- or nine-out-of-10 match. Transplants from such “mismatched” donors may be better than no transplant at all, but as studies like Milano and Delaney’s show, cord blood transplants may be the best option for some patients.

“This brings home the point that cord blood shouldn’t be called an alternative donor. The outcomes are the same as a conventional donor,” Delaney said. “This paper shows that if you’ve got high-risk disease and are at high risk for relapse post-transplant, transplantation from a cord blood donor may be the best option.”

For Day, none of the traditional donor sources were an option for her transplant. There were no HLA matches or near matches in her family or in the national donor bank, Be The Match. Day is mixed-race; minority donors and those of mixed race are especially underrepresented in the national pool of donors — and patients often won’t match the HLA type of a donor of a different racial or ethnic background.

Day had heard of cord blood transplants but didn’t know much about them until it became clear that was her best option. When they found a match for her in the cord blood database, “that was a big relief,” Day said. 

That period of waiting and testing was really tough, she said. It was a few months between when they’d started testing her family members and when they found her cord blood match. At one point, Day remembered, she asked her doctor what they would do if they couldn’t find a matched donor. He answered that she’d likely be OK for up to a year on maintenance chemotherapy, so they’d spend that time hoping for a new match to show up in the national bank.

“Not having a match was the scariest part,” Day said.

Where you are treated matters

As with many types of cancer, where leukemia patients are treated matters for their survival — this is especially true for those receiving cord blood transplants, Milano said. Patients who receive transplants through the Hutch’s Cord Blood Program have nearly a 70 percent overall survival rate, higher than the survival rates reported at other centers.

“It’s pretty remarkable,” Milano said.

Delaney said she often hears of cases where patients are told they have no match among traditional donors and no other options. She hopes more patients and doctors will consider cord blood transplants — at a clinic with the right expertise and track record.

“Cord blood transplant is highly specialized and you want to be at an experienced center,” she said. “It is nuanced.”

The credit for the high survival rate is due not just to the research, Milano said, but to the nursing staff and other clinicians at the SCCA and the University of Washington Medical Center.

“They know how to take care of patients,” Milano said. “The institution makes a difference.”

Rachel Tompa is a former staff writer at Fred Hutchinson Cancer Center. She has a Ph.D. in molecular biology from the University of California, San Francisco and a certificate in science writing from the University of California, Santa Cruz. Follow her on Twitter @Rachel_Tompa.

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