Allogeneic transplant: The 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 from other people as foreign, too.

If the tissue type match between donor and recipient is not close, the patient’s immune system may see the new stem cells as foreign and destroy them. This is called graft rejection, and it can lead to graft failure. This is rare, because the pre-transplant treatment (chemo and/or radiation) mostly destroys the recipient’s immune system, and donor matching is carefully done.

Another problem that can happen is that when the donor stem cells make their own immune cells, the new cells 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 called “Problems that may come up shortly after transplant” for details). The grafted stem cells attack the body of the person who got the transplant. This is a common problem, and it’s the main reason every effort is made to find the closest match possible.

HLA matching

Many factors play a role in 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 a number of pairs of HLA antigens. We inherit one of each of these pairs from each of our parents (and pass one of each pair on to each of our children). Doctors try to match these antigens when finding a donor for a person getting a stem cell transplant.

How well the donor’s and recipient’s HLA tissue types match plays a large part in whether the transplant will work. A match is better when all 6 of the known major HLA antigens are the same — a 6 out of 6 match. People with these matches have a lower chance of graft-versus-host disease, graft rejection, having a weak immune system, and getting serious infections. For bone marrow and peripheral blood stem cell transplants, sometimes a donor with a single mismatched antigen is used — a 5 out of 6 match. For cord blood transplants a perfect HLA match doesn’t seem to be as crucial for success, and even a sample with a couple of mismatched proteins may be OK.

Doctors keep learning more about better ways to match donors. Today, fewer tests may be needed, for siblings since their cells vary less than an unrelated donor. But on unrelated donors, more than the basic 6 HLA antigens are often tested to reduce the risks of mismatched types. Sometimes doctors will want to look at 5 pairs of antigens, for example, to try and get a 10 out of 10 match. Certain transplant centers require higher levels of matching. Other centers are doing clinical trials with related half-matched donors and different chemotherapy schedules. This is an active area of research because it’s often hard to find a good HLA match.

Finding a match

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. If possible, the search for a donor usually starts with the patient’s brothers and sisters (siblings), who have the same parents as the patient. The chance that a sibling would be a perfect match (that is, that you both received the same set of HLA antigens from each of your parents) is about 1 out of 4.

If a sibling is not a good match, the search could then move on to relatives who are less likely to be a good match — parents, half siblings, 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’s possible to find a good match with a stranger. Your doctor will help you do this. To help with this process, bone marrow transplant registries are used (see the “To learn more” section). Registries serve as matchmakers between patients and volunteer donors. They can search for and access millions of possible donors and hundreds of thousands of cord blood units. The largest registry in the United States is Be the Match (formerly called the National Marrow Donor Program). Another agency, the Caitlin Raymond International Registry, has access to millions of international records, too. These agencies have successfully matched thousands of donors and recipients.

The chances of finding a matched unrelated donor improve each year, as more volunteers sign up. Today, about half of white people who need a stem cell transplant may find a perfect match among unrelated donors. This drops to about 1 out of 10 people in other ethnic groups, mostly because their HLA types are more diverse and they are less likely to take part in donor registries. Depending on a person’s tissue typing, several other international registries also are available. Sometimes the best matches are found in people with a similar racial or ethnic background. Finding an unrelated donor can take months, though. A single match can require going through many, many records.