Afterbirth No Longer an Afterthought: Cord Blood for Cancer Patients
A gentle smack on the bottom, a quick whisk to the warming table for cleanup, and sighs of relief fill the room. A baby is born. New life has come into the world. But the potential for life doesn't rest only with the infant. In the umbilical cord and placenta, leftover blood capable of regenerating tissue is helping doctors to treat cancer patients.
Months before birth, stem cells travel from the fetal yolk sac to the baby's bone marrow where they are ready to replace red blood cells, immune cells, and platelets after birth. In the fetus, the stem cells circulate until the time of birth. After the umbilical cord is cut, cells remaining in the placenta may be collected and frozen for later use.
Like the stem cells that patients receive in bone marrow transplants, these cord blood stem cells can be injected into another person to repair damage caused by radiation or chemotherapy, migrating to the recipient's bone marrow in a process called engraftment.
"The limits of cord blood have yet to be defined," says Dr. Ron Gress, who heads the Transplantation Therapy Section of the Experimental Transplantation and Immunology Branch in NCI's Center for Cancer Research, "but the field has moved far enough forward that we know cord blood as a source of stem cells for transplantation is a viable treatment possibility."
The immune system attacks transplanted tissues when antigens on the new cells' surfaces are too different from those of native tissue. In turn, transplanted immune cells can attack a recipient's body in a condition known as graft-versus-host-disease (GVHD). This is why finding a matched donor is so important in transplantation.
Less than a third of patients who need bone marrow transplants are able to find an ideal match - a blood relative with the same human leukocyte antigens (HLAs) - in time to have the procedure. The next best option is an unrelated matched donor. For African Americans, Asians, and people from other minority groups, this process is particularly restricted because the pool of donors from similar ethnic backgrounds is so small. But there's data to indicate that cord blood could solve many of these problems.
Unlike bone marrow, cord blood is easy to get and poses no harm to the donor. Cord blood is also almost always free of viruses or bacteria, and appears to be more "recipient friendly" because units only need to match in four out of six HLA categories. In additon, there's lower incidence of GVHD than in bone marrow recipients.
The clinical potential is so great that, after receiving recommendations in a report from the Institute of Medicine, Congress passed legislation to increase the nation's inventory of cord blood for use in transplantation. The first contracts for blood banks to begin implementing the plan will be announced by the Health Resources and Services Administration before the end of this fiscal year.
"Cord blood transplants are already the standard practice in Japan, and in Europe and the U.S., the approach is steadily being adopted," says Dr. John Wagner, a pioneer in the field of cord blood transplantation at the University of Minnesota. "Once we begin receiving reports from the U.S. and Europe that document results similar to ours, I think that use of cord blood will dramatically change for adults as well as children."
Much of Dr. Wagner's results come from studies in adults with leukemia. Beyond showing that cord blood transplants can work, researchers have found that HLA-mismatched cord blood units actually attack the cancer, decreasing the chance of relapse. While HLA-mismatching carries a higher risk of transplant-related mortality, new information suggests that this can be minimized by increasing the number of transplanted cord blood cells. "While survival after HLA-mismatched cord blood parallels that of HLA-matched marrow, we continue to look for ways to make it better," says Dr. Wagner.
Then why aren't cord blood transplants standard practice in the United States today for adults? The principal limiting factor is cell dose - the number of cells given to a patient based on body weight. Cord blood is a rich source of stem cells, but the number of cells in the collection is often small. Adults need at least 25 million nucleated cells per kilogram of weight for successful engraftment, and very few of the cord blood units available today through blood banks meet this criterion. As a result, most of the 8,000 transplants conducted during the past 16 years have been in children, whose body weight is generally lower than that of adults.
To overcome this barrier, researchers are combining two individual cord blood units to increase the number of transplanted cells. "For patients who have received a double cord-blood transplant, we have observed a greater chance of survival compared with single-unit transplants," Dr. Wagner says. "While we expected to see less transplant-related mortality with the higher cell dose, we were surprised to see a markedly lower risk of relapse in patients transplanted with two cord blood units."
Dr. Wagner's team has performed nearly 300 double cord-blood transplants in adults and children so far, with 76 percent mismatched at 2 HLA antigens. The next step is to determine how results compare in patients transplanted with two cord blood units versus HLA-matched marrow.
Beyond testing double cord-blood transplants, Dr. Wagner's group is also looking into cord blood-derived natural killer cells in patients with refractory leukemia, cord blood-derived regulatory T cells to enhance engraftment and reduce GVHD, and injection of cord blood right into the bone marrow space to speed marrow recovery.
By Brittany Moya del Pino