New Promise in Stem Cell Transplants for Blood Cancer Patient
For many patients with particularly aggressive and/or relapsed blood cancers, the best chance of cure is very high-dose therapy. Because these high doses kill normal blood cells along with the cancer cells, patients must receive healthy blood stem cells in the form or a hematopoietic stem cell transplant (HSCT) in order to survive the high-dose treatments.
Originally, HSCTs used stem cells from bone marrow (BM) sources. More recently, peripheral blood has been increasingly used as a source for HSCTs. And a report now shows that umbilical cord blood (UCB) may have real advantages as a stem cell source.
It has been known for some time that allogeneic transplants (transplants from donors) are more likely to provide long-term cancer-free survival. This is because the normal blood stem cells transplanted from another individual (grafts) not only replace critical blood cells lost during pre-transplant chemotherapy, but can also attack remaining cancer cells. This is known as the "graft-versus-tumor" effect and it substantially reduces relapse risk.
Unfortunately, transplants come with substantial risks, as I have discussed here before. The high-dose radiation and/or chemotherapies can be intolerable for some patients, especially those over the age of 50 and younger patients with confounding health issues. Serious infections can afflict patients until the normal immune cell graft is able to take over. And when allogeneic transplant donors are not well-matched, patients can develop life-threatening graft-versus-host disease (GvHD), in which transplanted immune cells attack a patient's normal cells as well as the cancer cells.
In general, the best ratio of good to bad effects comes in transplants with well-matched siblings as stem cell donors. But only 30 percent of transplant candidates have such a donor available. To avoid GvHD, transplants can use healthy blood cells collected from the patient before he or she undergoes aggressive treatment, a procedure called an autologous transplant. But cancer cells must be efficiently removed before the stem cells can be safely given back to the patient, and the patient's own stem cells provide little if any "graft-versus-tumor" effect since they are so highly related.
New Techniques Offer Hope
I have written about new transplant procedures that use targeted pre-transplant therapies to reduce side-effects, the so-called "mini transplants" being developed by Society-sponsored researchers in Seattle, WA. And I have described the exciting results of a Society-sponsored Philadelphia research group that has learned how to help immune cells do a better job fighting infections after an autologous transplant. Both teams, funded by Society Specialized Center of Research grants, are now working to extend their findings and into improving anti-tumor effects after allogeneic transplants without increasing GvHD.
UCB transplants have been used since the early 1990s. Cords are potentially available from every new birth and cells can be recovered and stored frozen until needed. In the United States, there are now 13 UCB cell banks overseen by the National Marrow Donor Program, with 34,707 cryopreserved UCB units currently listed. Around the world, the number of unrelated UCB transplants in children and adults has increased dramatically to more than 10,000, with more than 300,000 UCB grafts available from more than 40 banks. Early research data suggest that UCB transplants do not need to be as well-matched as transplants from other sources, perhaps because the blood cells from newborns are naturally less mature and less able to mount the immune responses that can cause GvHD.
Mary Eapen, M.B.B.S., D.C.H., M.R.C.P.I., M.S., and her colleagues recently compared umbilical cord blood with bone marrow as stem cell sources for 503 children with acute leukemia. Their sea-change study was just published in a prestigious medical journal, The Lancet.
Transplant matches are typically made based on a series of six to eight different blood cell proteins called HLA. Dr. Eapen's group found that children given a highly-matched unrelated BM graft (comparable to a good sibling match) had no better relapse-free survival than the children who received one or two HLA-mismatched UCB transplants. In fact, mismatched BM recipients were more prone to GVHD and no less likely to relapse than mismatched UCB recipients, providing UCB recipients with better outcomes. These findings suggest that finding a "good" match will be easier with UCB sources.
However, transplant-related mortality was higher in children transplanted with a low UCB cell-dose and one HLA-mismatch. So these investigators recommend that UCB grafts should contain a certain minimum cell dose. At present, available cell numbers do limit the utility of UCB transplants, especially for adult patients. But Society-funded researchers are working to resolve these problems. UCB transplants may soon provide the safe and highly effective treatment alternatives for the large number of blood cancer patients who need them.
Read more about stem cell transplants on the Society Web site. Ongoing Society-funded research in this area is taking place at:
Deborah Banker, Ph.D.