miércoles, 31 de octubre de 2012

Study Urges Caution on Source of Unrelated Donor Stem Cell Transplants ▲ NCI Cancer Bulletin for October 30, 2012 - National Cancer Institute

NCI Cancer Bulletin for October 30, 2012 - National Cancer Institute


Study Urges Caution on Source of Unrelated Donor Stem Cell Transplants

Transplant recipient Teresa Hurtado-Diaz and her donor Lydia Gonzalez (Courtesy of the National Marrow Donor Program)Transplant recipient Teresa Hurtado-Diaz (left) of Windsor, CA, and her donor Lydia Gonzalez (right) of Beeville, TX. (Courtesy of the National Marrow Donor Program)
The first randomized trial comparing bone marrow and peripheral blood stem cells (PBSCs) as sources for hematopoietic stem cell transplants from unrelated donors suggests that caution may be needed when using PBSCs from unrelated donors to treat leukemia or related blood disorders. The results were published October 18 in the New England Journal of Medicine.
Use of PBSCs from related and unrelated donors has skyrocketed in the last decade, largely due to the preference of transplant doctors, explained Dr. Dennis Confer, chief medical officer of the National Marrow Donor Program Exit Disclaimer and the study’s senior author.
Currently, about three-quarters of all transplants from unrelated donors use PBSCs, as opposed to bone marrow. PBSC transplants engraft more rapidly than bone marrow but come with a potential downside: they contain large numbers of T cells, a type of immune cell that can trigger graft-versus-host disease (GVHD). In this condition, donor immune cells attack tissues and organs in the recipient’s body.
In clinical trials comparing outcomes in patients transplanted with PBSCs or bone marrow from related donors, the incidence of GVHD was sometimes higher with PBSCs than with bone marrow but not enough to deter their use. But the incidence of GVHD is higher with transplants from unrelated donors than with those from related donors, and until now no large trial had directly compared the safety and effectiveness of the two stem-cell sources from unrelated donors.
“We had multiple trials [of bone marrow versus PBSCs] in the related-donor setting that were randomized, international, had large numbers [of patients], and had very conclusive results, and we made the jump to the unrelated setting without having any of that knowledge,” explained Dr. Stephanie Lee, a transplant doctor and GVHD researcher at Fred Hutchinson Cancer Research Center and a co-author of the study. “It wasn’t a huge leap, but we didn’t have any randomized trial data about the risks and benefits of one source versus another in that particular setting.”
Tradeoffs between Graft Sources
The researchers, led by Dr. Claudio Anasetti of the H. Lee Moffitt Cancer Center, enrolled 551 patients in the randomized trial. All had high-risk leukemia or a chronic myeloid disorder and an unrelated stem cell donor. The patients were randomly assigned to receive either PBSCs or bone marrow stem cells. Ninety percent of the patients received a transplant of the graft source to which they were randomly assigned. The primary endpoint of the trial was overall survival at 2 years.
Instead of being the default choice for most unrelated-donor transplants, mobilized peripheral blood stem cells should be used in only the minority of patients for whom the benefits outweigh the risks.

—Dr. Frederick R. Appelbaum
Two years after transplantation, 51 percent of the patients who received peripheral blood stem cells were alive, compared with 46 percent of patients who received bone marrow stem cells. This difference was not statistically significant, meaning that it could not be ruled out as being caused by chance alone. Rates of relapse also did not differ between the two groups.
Additional analyses, however, showed that other outcomes did differ. Fewer patients who received peripheral blood stem cells experienced graft failure, in which the donor cells die and fail to form a new blood cells for the patient, than those who received bone marrow (3 percent versus 9 percent). Eleven patients who received bone marrow died from graft failure, compared with none of those who received PBSCs.
However, substantially more patients who received peripheral blood stem cells developed chronic GVHD within 2 years after transplant than those who received bone marrow (53 percent versus 41 percent). Thirty patients who received peripheral blood stem cells died of chronic GVHD versus 14 who received bone marrow.
Of the patients alive after 2 years, more of those who received peripheral blood stem cells needed to take drugs to suppress the immune system due to GVHD than those who received bone marrow (57 percent versus 37 percent).
Causes of Death over Two Years of Follow-Up*
 Peripheral Blood Stem CellsBone Marrow
 %No. of Patients%No. of  Patients
Disease relapse48695073
Graft failurenonenone811
Acute GVHD**17241420
Chronic GVHD21301014
Other causes10141014
*290 out of the 513 patients who received their randomly assigned transplants died during the first 2 years after treatment
**GVHD occurring in the first few months after transplant
“It is…possible that increased mortality from chronic GVHD among recipients of peripheral blood stem cells from unrelated donors offsets the benefits associated with the more rapid and robust engraftment that occurs with peripheral blood stem cells, as compared with bone marrow,” wrote the authors.
Different Risk Factors, Different Sources
The researchers suggest that specific characteristics of individual patients may guide the use of one stem cell source over another. For example, patients at high risk of graft failure may benefit from PBSCs, and bone marrow would likely be recommended for other patients, especially those whose immune systems are already suppressed due to prior chemotherapy and who consequently have a lower risk of graft rejection.
As prophylaxis and treatment for GVHD improve, peripheral blood stem cells will likely remain favored over bone marrow.

—Dr. Richard Little
“[These] results provide data that should change current practice. Instead of being the default choice for most unrelated-donor transplants, mobilized peripheral blood stem cells should be used in only the minority of patients for whom the benefits outweigh the risks,” wrote Dr. Frederick R. Appelbaum of the Fred Hutchinson Cancer Research Center in an accompanying editorial.
Dr. Richard Little, an investigator with NCI’s Cancer Therapy Evaluation Program, agreed, with one caveat: “As prophylaxis and treatment for GVHD improve, peripheral blood stem cells will likely remain favored over bone marrow,” he said.
GVHD treatment and prevention is not the only “moving target” in transplantation research, added Dr. Lee. People are also experimenting with different sources of donor cells and with reduced-intensity conditioning regimens, which do not completely kill the host’s immune system before transplant, she explained. “Transplant [research] is moving so quickly, it’s kind of hard to come up with a result that’s then applicable for many, many years afterwards.”
And, although the researchers expressed concern that donor preference is helping to drive the choice of stem-cell source, Dr. Confer doesn’t see that as a major deciding factor. “The donors are very altruistic, and they’re very interested in helping the patients they’re matched with. If the transplant doctor asks for bone marrow or peripheral blood stem cells, the vast majority of donors will do whatever that doctor thinks is best for the patient,” he concluded.
Sharon Reynolds
This research was supported in part by a grant from the National Institutes of Health (U10HL069294).
National Marrow Donor Program
The first hematopoietic stem cell transplantation from an unrelated donor to treat leukemia was performed in 1979. Since then, rapid improvements in the technique and burgeoning databases of people willing to donate life-saving stem cells to strangers have led to thousands of transplants from unrelated donors being performed each year in the United States alone.
The National Marrow Donor Program Exit Disclaimer, a nonprofit organization in the United States, operates the world's largest database of cord blood donors and potential marrow donors and has facilitated more than 50,000 transplants over the last 25 years. But more volunteers are always needed.
Currently, the registry has a particular need for younger donors (ages 18 to 44) and donors from underrepresented racial groups, such as African Americans, Asians, and Native Americans.
More information on how to be a stem-cell donor can be found online Exit Disclaimer .

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