Unrelated Donor Program for Pediatric Bone Marrow Transplant

When a histocompatible, related donor cannot be found, an alternative is to identify unrelated, healthy individuals who are histocompatible with the patient and are willing to donate bone marrow stem cells.

The first marrow transplant from an unrelated donor was reported in 1979. In a review of the initial 462 transplants using unrelated donors, 66 percent were complete matches, while 34 percent were partial matches. In those receiving human leukocyte antigen (HLA) matched marrow from unrelated donors, 64 percent developed moderate to severe acute graft-versus-host disease (GvHD) and 55 percent developed chronic GvHD.

More recently, there have been significant advances in HLA typing technology. The genes that are responsible for making the HLA antigens in the body have been identified and studied. At UCSF Benioff Children's Hospital, we routinely evaluate the precise characteristics of each of the 10 major HLA genes in both the patient and in all potential donors. The availability of this type of high resolution DNA typing and the increase in size of the donor database, has resulted in not only a significant increase in the number of donors but also the ability to look for the best possible match. With this approach it appears that the severity of moderate to severe acute GvHD has been reduced and is more easily treatable.

The National Marrow Donor Program (NMDP) is a nonprofit organization that facilitates life-saving blood stem cell transplants for patients who do not have a donor in their family. The NMDP manages the world's largest registry of volunteer stem cell donors and cord blood units.

The NMDP maintains the world's largest, most diverse registry of more than 5 million volunteer blood stem cell donors and more than 28,000 cord blood units, as of July 2003. With so many potential donors, the likelihood of finding a match has increased dramatically for patients from all racial and ethnic groups. Nevertheless, even with millions of potential donors on the Registry, some patients are unable to find a match because of the rarity of their tissue traits. The need remains for more potential donors.

The NMDP works with families, communities, businesses and other groups to raise awareness and recruit committed individuals to join the Registry. Recruitment efforts focus on increasing the diversity of tissue types available and registering people who are committed to helping any patient in need.

To learn more about the National Marrow Donor Program, visit marrow.org or call (800) MARROW-2 or 800-627-7692.

Bone marrow stem cells can be collected from the blood that circulates throughout the body. When healthy people are treated with a type of chemical normally made in small amounts in the body called granulocyte colony stimulating factor (G-CSF), increased numbers of stem cells leave the marrow and enter the blood stream. These cells, referred to as peripheral blood stem cells (PBSC) can be collected along with other white cells by a process called leukapheresis.

For the past 15 years, leukapheresis has been used routinely for patients with cancer to donate their own cells that will be transplanted after they have undergone therapy to remove the cancer. Recently, it has been used for collecting bone marrow stem cells from healthy donors for transplantation into related or unrelated recipients.

The advantages of a PBSC collection for the donor is that it offers the opportunity to:

Avoid a surgical procedure in an operating room, thus eliminating anesthesia risk
Recover immediately
Obtain as much as 10 times the number of CD34 positive bone marrow stem cells that can be collected in a typical marrow harvest

The disadvantages of PBSC transplants for the donor are the four to five days of G-CSF injections that cause bone pain, and the possible need for placement of a temporary catheter in one of the large veins in the neck or groin area. In most cases, the pain responds to treatment with Tylenol and/or non-steroidal, non-narcotic medications. Approximately 3 percent of normal donors treated with G-CSF have symptoms sufficiently severe to require discontinuation of the drug.

The potential risk of a PBSC transplant to the recipient is an increased incidence of chronic GvHD compared to a bone marrow transplant. However, this may be associated with a lower incidence of leukemic relapse. However, because of this risk, we currently only offer PBSC transplants for patients with cancers including leukemia, myelodysplastic syndromes (MDS) or histiocytosis, in which some GvHD may be of potential advantage, or those situations in which a large number of bone marrow stem cells are needed and can be more readily obtained from the blood.

At this point in time, all of the advantages and disadvantages of PBSC transplants compared to standard bone marrow transplants have not been fully identified and research into this source of bone marrow stem cells in ongoing.

If a matched unrelated marrow stem cell donor is unavailable, another source of unrelated donor bone marrow stem cells is umbilical cord blood (UCB), which may be considered. There are over three-dozen UCB registries worldwide that process and store cord blood collections from healthy babies. The NMDP is trying to coordinate the search process through as many of these independent registries as possible. Currently, the NMDP has access to close to 200,000 UCB units.

The cord blood, which is normally thrown away after a baby is born, contains a relatively large number of bone marrow stem cells. One potential advantage of using cord blood is that it does not need to be a perfect tissue match with the recipient. Disadvantages include the limited number of cells in a collection and relative delay in the recovery of marrow function after transplant.

The UCSF Pediatric BMT Program uses unrelated cord blood for transplantation as an alternative source of bone stem cells when a matched unrelated marrow donor is not available. In addition to having participated in the National Institutes of Health (NIH)-sponsored national collaborative study of cord blood transplantation in children (COBLT), the UCSF protocol permits the use of cord blood for any eligible patient with any disease for which a BMT is indicated.

UCSF Benioff Children's Hospitals medical specialists have reviewed this information. It is for educational purposes only and is not intended to replace the advice of your child's doctor or other health care provider. We encourage you to discuss any questions or concerns you may have with your child's provider.