ACS :: Allogeneic Transplant: Importance of a Matched Donor

The immune system plays an important role in the success of any allogeneic stem cell transplant. The immune system normally keeps us healthy by destroying anything in the body it sees as foreign, such as bacteria or viruses. A working immune system recognizes cells coming from other people as foreign, too.

If the tissue type match between donor and recipient is not close, the recipient's immune system may see the new stem cells as foreign and destroy them. This is called graft rejection. Usually this doesn't happen because the pre-transplant treatment (chemo and/or radiation) damages the immune system. What can happen is the donor stem cells make their own immune cells, which means they may see the patient's cells as foreign and turn against their new home. This type of attack is called graft-versus-host disease (see "Graft-versus-host disease" in the section "Problems After Transplant"). The grafted stem cells attack the host recipient. To avoid this, every effort is made to find the closest match possible.

Many factors determine how the immune system knows the difference between "self" and "non-self," but the most important for transplants is the human leukocyte antigen (HLA) system. Human leukocyte antigens are proteins found on the surface of most cells. They make up a person's tissue type, which is different from a person's blood type.

Each person has 3 pairs of major HLA antigens (known as A, B, and DR), for a total of 6 antigens. We inherit 1 set of A, B, and DR antigens from each of our parents (and pass 1 of our 2 sets on to each of our children).

How well the donor's and recipient's HLA tissue types match plays a large part in determining whether the transplant will be successful. The best matches are where all of the HLA antigens are the same -- a 6 out of 6 match. These have a lower chance of rejection or GVHD. For bone marrow and peripheral blood stem cell transplants, often a 5 out of 6 match may be used. For cord blood transplants a perfect HLA match doesn't seem to be as crucial for success, and even a 4 out of 6 match may be OK.

There are thousands of different combinations of possible HLA tissue types. This can make it hard to find an exact match. HLA antigens are inherited, so the search for a donor usually starts with the patient's brothers and sisters (siblings), if possible. The chance that any sibling would be a perfect match (that is, that you both received the same set of HLA antigens from each of your parents) is 1 out of 4.

If a good match is not found in a sibling, the search may then move on to relatives who are less likely to be a good match -- parents and extended family, such as aunts, uncles, or cousins. (Spouses are no more likely to be good matches than other people who are not related.) If no relatives are found to be a close match, the search then widens to the general public.

As unlikely as it seems, it is possible to find a good match with a stranger. To help with this process, bone marrow transplant registries are used (see the "Additional resources" section). Registries serve as matchmakers between patients and volunteer donors. The largest registry in the United States is the National Marrow Donor Program. It lists the tissue types of more than 5 million volunteer donors and about 30,000 cord blood units. Another agency, the Caitlin Raymond International Registry, has access to millions of international records. These agencies have successfully matched thousands of donors and recipients. Depending on a person's tissue typing, several other international registries also are available.