Researchers at the Fred Hutchinson Cancer Research Center have found a way to make umbilical cord blood transplants safer and more effective. The technology, developed in the lab and being tested in a phase I clinical trial of leukemia patients, expands the number of stem cells in a unit of cord blood to give patients a safer, more rapid engraftment and recovery after a transplant.

The research -- published this week in Nature Medicine and supported by grants from the American Cancer Society, National Institutes of Health (NHLBI), and the Damon Runyon Cancer Research Foundation -- offers potential promise to leukemia patients in need of intensive treatment.

Advantages of umbilical cord blood

Leukemia is a type of cancer that begins in the bone marrow, the soft inner part of bones where new blood cells are made. It strikes both adults and children. Chemotherapy and other drugs are often used to treat leukemia. Because the high doses of chemotherapy needed to kill the leukemia cells often destroy the bone marrow as well, many patients also need a blood stem cell transplant to basically create new bone marrow. In this procedure, stem cells (the cells that give rise to new blood cells) are removed from a donor's blood or bone marrow and transplanted into the patient.

Transplants are most successful when the stem cells come from a donor whose cells are similar to the patient's -- usually a brother or sister or other relative. If a patient doesn't have a relative who is a good match, the only other option is to look for matching donors in national and international databases.

"While over 10 million people are listed as donors, up to 30% of people still can't find a match," said lead author Colleen Delaney, MD, Cord Blood Transplant Director and Assistant Member of the Clinical Research Division at the Fred Hutchinson Cancer Research Center. Delaney also serves as Assistant Professor in the Department of Pediatrics at the University of Washington Medical School. "Their chances are even lower if they're of an ethnic or mixed race background."

Another potential source of stem cells is blood from umbilical cords, which can be collected after a baby is born. Umbilical cord blood is a rich source of stem cells.

"Cord blood is readily available as it is collected at the time of birth and then stored until future use. Even better, because umbilical cord blood has a naïve immune system, it does not need to be as stringently matched to the patient and therefore we can identify a cord blood donor in approximately 99% of patients who can’t find a conventional donor," said Delaney. "However, it has a huge disadvantage in that the units are so small."

Because it is difficult to get enough stem cells from umbilical cord blood to successfully treat an adult, cord blood has mostly been limited to use in children. Even when it is used, the small number of stem cells in the blood means that it takes a long time, often about a month, for the cells to create enough new blood cells. Making enough new white blood cells is especially important, as these are the main cells that help the body fight off germs. Without enough white blood cells, a person is at risk for life-threatening infections.

Expanding cord blood cells

Initially, Delaney says, researchers were hopeful that perhaps using the blood from 2 umbilical cords would solve the problem. However, using that technique still required a lot of time for blood cell counts to recover – time patients with compromised immune systems didn't have.

Delaney and her colleagues instead built on the work of Irwin Bernstein, MD, a member of the Hutchinson Center’s Clinical Research Division, who in 2000 discovered a way to expand stem cells by activating the Notch signaling pathway in the cells. By manipulating that pathway, Delaney and colleagues were able to optimize and expand the number of stem cells in the cord blood in the lab. They then infused high-risk leukemia patients with the cells in a phase I clinical trial.

The results were very promising. For the 10 patients reported in the study, it took an average of 14 days for the stem cells to engraft and make enough new white blood cells, compared to an average of about 4 weeks using cells that had not been expanded.

“The real ground-breaking aspect of this research is that we have shown that you can manipulate stem/progenitor cells in the lab with the goal of increasing their numbers. When given to a person, these cells can rapidly give rise to white blood cells and other components of the blood system,” said Delaney.

The age range of the patients was from 3 to 43. The high-dose chemotherapy regimen given to prepare the body for the stem cell transplant can be risky in patients over 45 years old, Delaney says.

While early results are encouraging, the researchers say the technique needs to be replicated in randomized trials and tested in other centers.

Delaney is still enrolling patients in the trial, which she hopes to soon move to phase II. She also hopes to soon ship the technology to other research centers. Currently, it is only available at Fred Hutchinson.

"People should be hopeful that they will be able to get a transplant even if they can't find a donor," said Delaney.

Citation: "Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution." Published January 17, 2010 in Nature Medicine. First author: Colleen Delaney, MD, Fred Hutchinson Cancer Research Center.

Reviewed by: Members of the ACS Medical Content Staff