Types of Donors

One of the first evaluations done for patients who are being considered for a BMT involves special blood studies on the patient and his or her entire family in order to decide who is the best donor. The standard test is called tissue typing (also referred to as HLA or histocompatibility typing). A second test, which has recently been developed, is called high resolution DNA typing. These tests gauge how much the donor and recipient cells will recognize one another as the same or different. The greater the differences in the HLA typing, the greater the chance that either the donor's cells will not grow in the recipient (rejection or graft failure) or they will attack the recipient and cause a reaction called graft vs. host disease (GVHD).

The optimal donor: HLA matched

The optimal donor is an HLA matched (histocompatible) relative who is usually a sibling or, in rare cases, a parent or grandparent with identical HLA tissue typing. HLA matched (histocompatible) donor-recipient pairs are always identical by high resolution DNA typing.

Everyone inherits two sets of chromosomes containing HLA genes (4 genes per set), one set from their father and one from their mother (a total of 8 genes). There is a one in four (25%) chance that any brother or sister will have inherited the same two sets of HLA genes as the patient. For a parent to be "matched" with his or her child, both parents must by chance have some HLA genes in common with each other. It is very unlikely (1 in a million) for two unrelated individuals to have the same HLA genes in common, and there is only a 1 in 200 chance that a parent and child will be HLA matched.

Partially-matched (haplocompatible) relative

A biologic parent is always half matched (i.e., haplocompatible,or 4 out of 8 HLA match) with his or her child since each child inherits half of the HLA genes from each parent. There is a 50% chance that any sibling will be haplocompatible with any other sibling. In order for a haplocompatible bone marrow transplant to work without resulting in a fatal GVHD reaction, the stem cells must be specially treated after they are collected from the donor and before they are transplanted into the patient. This treatment depletes them of the donor T lymphocytes that cause GVHD (T cell depletion).

There are advantages and disadvantages to T cell depletion. The technique that is used at the UCSF Pediatric BMT Program significantly reduces the risk of GVHD both in terms of its chances of occurring, as well as its severity if it does occur. However, there is an added risk that the marrow might not engraft. In order to improve the chances for successful engraftment (>95%), additional treatment with radiation and chemotherapy) must be added to the conditioning regimen in most cases (except for children with severe combined immunodeficiency disease or SCID). Also, there may be a delay in the recovery of the immune system (the body's defense against infection) resulting in a higher risk of infections after transplant. T cell depleted bone marrow stem cells from a parent or sibling may be considered for children who do not have an HLA matched related or unrelated donor. For more information about this special program at UCSF see haplocompatible relatives.

Autologous donor

For some types of cancers (for example, brain tumors, neuroblastoma, lymphomas, sarcomas, Wilm’s tumor, and PNET) it is possible to use the patient's own (autologous) marrow stem cells (bone marrow or peripheral blood) for the transplant.

If bone marrow stem cells are going to be used, prior to admission for the transplant (a few days to many months), a portion of the patient's marrow is harvested in the operating room under general anesthesia and frozen in liquid nitrogen in the Pediatric Bone Marrow Transplant Laboratory. Prior to freezing, the marrow may need to be treated to remove cancer cells that may still be present. Following the conditioning period, the stored marrow is thawed and transfused into the patient. While one advantage to this type of transplant is the absence of GVHD, a potential disadvantage is the greater risk that the cancer will recur.

If possible,  peripheral blood stem cells are now used for autologous transplants.  Prior to admission for the transplant, the patient’s stem cells are collected using a special process called leukapheresis. During this procedure the patient’s blood is passed through a machine which collects the portion of white cells containing bone marrow stem cells. The remaining white cells, red cells, and platelets are given back to the patient. Placement of a special intravenous line, (double lumen pheresis catheter), may be necessary for this procedure. In preparation for the leukapheresis, the patient receives a drug or cytokine called G-CSF for 3-4 days to encourage stem cells to leave the marrow and enter the blood. Occasionally, after many cycles of chemotherapy and/or local radiation therapy G-CSF is inadequate to "mobilize" a sufficient number of bone marrow stem cells into the blood. We are currently evaluating a new approach using a combination of cytokines. Preliminary results are promising.

Unrelated donor

When a matched relative is unavailable and there is time to conduct a search, an unrelated donor is usually considered. The chances of any 2 unrelated individuals being matched for all 8 HLA genes is 1 in a million. The National Marrow Donor Program (NMDP) was established in 1986 to create a large computer database containing the HLA types of volunteer donors. As of August 1998, there were over 4 million potential donors registered with the NMDP worldwide. The chances of finding a matched donor through the registry vary from 20-60% depending on the patient's ethnic background. It may take 6 months (or longer) to identify a donor, however, and the added cost of using an unrelated donor may be as much as $30,000. Finally, even with a perfectly matched donor there is a significant chance that GVHD will occur and that it will be more severe than with a matched relative.

Umbilical cord blood

If a matched unrelated marrow stem cell donor is unavailable, another source of unrelated donor bone marrow stem cells, umbilical cord blood (UCB), may be considered. There are over three dozen UCB registries worldwide which process and store cord blood collections from healthy babies. 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 post-transplant.

You may learn more about the protocols at UCSF which utilize either unrelated donors or haplocompatible relatives in Specific Treatment Options.