WebMD Health News
Louise Chang, MD
Jan. 19, 2010 -- Leukemia patients who receive stem cell transplants from the umbilical cord blood of newborns are usually vulnerable to life-threatening infections for at least a month as their immune systems recover.
Now researchers from Seattle’s Fred Hutchinson Cancer Center may have found a way to dramatically shorten this recovery period and reduce infection-related deaths.
In a small, early study, the researchers were able to successfully manipulate umbilical cord-derived stem cells to speed the production of infection-fighting white blood cells.
It took about two weeks for the transplanted cells to start making white blood cells on their own -- a process known as engraftment -- compared to a month when patients got the non-manipulated cord blood.
The research appears in the Jan. 17 issue of the journal Nature Medicine.
“If we really can make stem cell sources better, this may mean we would have donors for pretty much everyone who needs a transplant,” study researcher Colleen Delaney, MD, tells WebMD.
Stem cell transplants are performed in some patients with leukemia and other blood cancers to help the body make new blood cells after its own blood cells have been destroyed by disease or cancer treatments.
But cord blood contains only about one-tenth of the stem cells found in bone marrow, and this is why cord blood transplants usually take so much longer to engraft.
The advantage of cord blood transplants is that they do not need to be as perfectly matched to the patient as bone marrow transplants.
Close to one in three patients -- and as many as 95% of non-white patients -- who could benefit from a stem cell transplant never find a suitable match.
Researchers have long sought ways to increase the number of stem cells in cord blood in an effort to speed the production of infection-fighting white blood cells.
In the new research, the Fred Hutchinson researchers manipulated a system known as the Notch signaling pathway, which is involved in embryonic development.
By engineering a protein that activated the pathway, the researchers were able to expand the number of stem cells in a single unit of cord blood about 164-fold -- from 200,000 stem cells per kilogram of body weight to 6 million.
In a phase I study, 10 leukemia patients were treated with one unit of non-manipulated cord blood and one unit manipulated in the lab.
It took 14 days for the manipulated stem cells to engraft versus four weeks for the non-manipulated cells.
“We have shown that we can decrease the time to engraftment,” Delaney says. “Now we have to show a clinical benefit to the patient.”
The researchers will attempt to do this in a much larger clinical trial.
If that trial is successful, Delaney says the approach may prove useful not just for the treatment of blood-related cancers, but for the treatment of other conditions where white blood cell counts are low.
Stem cell transplant expert James Gajewski, MD, of Oregon Health Sciences University, tells WebMD that the new research addresses one of two major issues surrounding umbilical cord blood transplants.
“Every other attempt to expand (cord blood) stem cells has basically failed,” he says. “This is really the first significant proof that these cells can be expanded, and this group should be commended for doing brilliant work.”
But he says it remains to be seen if cord-blood derived stem cells can adequately mature and become useful in the immune systems of adult patients.
"This study wasn’t designed to address this issue, but a longer, larger study should,” he says.
Even if larger studies are positive, it is still not clear if stem umbilical cord blood transplants will ever be commercially viable, he says.
The banks that store umbilical cords are funded by the government. If government funding goes away, Gajewski says cord blood banks probably will too unless cord blood transplants prove useful for much more than the treatment of blood-related cancers.
“For the cord blood banks, the great hope for the future is that there will be many other uses for this treatment, such as repairing damaged hearts or livers,” he says. “But that is a long way away.”
SOURCES:Delaney, C. Nature Medicine, published online Jan. 17, 2010.Colleen Delaney, MD, division of clinical research, Fred Hutchinson Cancer
Center, Seattle.James Gajewski, MD, professor of medicine, Oregon Health Sciences
University, Portland.News release, Fred Hutchinson Cancer Research Center.American Cancer Society: “What is a Bone Marrow or Stem Cell
Transplant?”National Cancer Institute Fact Sheet: "BMT and Peripheral Blood Stem Cell
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