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Why is an HLA match needed for a successful transplant? (And how and why it works)

Jun 01, 2023 by Gift of Life News

When someone is diagnosed with a blood cancer or an immune system disorder, but treatments like chemotherapy do not work, their doctor may recommend a peripheral blood stem cell or bone marrow transplant as the best chance for a cure. The search then begins to find a matching donor. If a match cannot be found among family members, doctors can search the registry for an unrelated donor. 

Why does a transplant work when other treatments do not? 

Not every disease can be resolved through chemotherapy or radiation treatments. Sometimes cancer cells remain after treatment and start to regrow, and for other conditions, like sickle cell or inherited immune disorders, chemotherapy does not work – the only known cure is a transplant. 

The goal of a stem cell or marrow transplant is to completely replace the diseased or malfunctioning bone marrow with a new, healthy system that creates healthy blood cells and a fully functioning immune system.  

Why must the donor’s and recipient’s HLA match? 

Every person’s immune system protects the body from infections and diseases by differentiating cells that are “self” from those that are “not-self,” and killing the ones that are dangerous. This is the role of the Human Leukocyte Antigens (HLA) which are proteins on the cell surface that help identify each cell. 

When cells are transplanted from one person to another, if the HLA do not match, the transplanted cells will see the recipient as “not-self” and attack, causing “graft versus host disease.” The closer the HLA tissue types match, the more likely the transplant will be successful and the patient will recover. 

Since the basis of transplantation success is the HLA type, this is what we test for when you complete a cheek swab kit. The cheek cells that stick to the swab are analyzed by a laboratory to determine your individual HLA type. 

Some people believe that the donor and recipient need to have a matching blood type for the transplant, but that is not the case. Because the recipient will get the donor's blood-forming (hematopoietic) stem cells, those stem cells will start creating new blood cells identical to the donor's blood type. The recipient's blood type will change to match that of the donor. 

Why are everyone’s HLA different?

HLA types are inherited from our parents, and their parents, on back into the far reaches of your ancestry. Because new diseases arise constantly, the human immune system also adapts constantly, forming new HLA combinations from generation to generation to help fight off new illnesses. Over thousands of years, populations in different locations around the world developed distinct markers in their HLA profiles that may be less common in other populations, or even completely unique. There are millions of possible HLA combinations, so finding a match between two people is rare.

Since HLA are inherited, are relatives usually a match? 

Although the chances are higher of finding a match within the family, there is no guarantee. You are always a half-match with each of your parents, since you inherited half of your HLA from each of them. That means that parents and children are always half matches, but never a full match. You have a 25% chance of matching each one of your siblings (Click here to learn more about sibling matches).

Roughly 30% of patients are able to find a match with a family member, meaning 70% of them must rely on searches of the worldwide registry as their best chance of finding an unrelated donor. When we do find a full match on the registry, it is like winning the lottery! 

How is a match found in the registry?

If a patient does not have a matching sibling or relative who can donate, their medical team will search the worldwide marrow donor database in the hope of finding an unrelated donor. They do this by entering the patient’s HLA profile, and the software will look for profiles that share the closest HLA to the search criteria. With luck, the results will find one or more possible donors with a an HLA match. 

If one or more potential donors are found in the database, the next step is to run a new HLA test for the potential donors, using either a swab kit or a blood draw to ensure that the HLA profile is correct. The transplant physician will carefully select the prospective donor that is the best match for the patient, and once the donor is requested, the registry reaches out to schedule the donation. 

How many people are in the worldwide registry? 

The worldwide registry, currently with more than 41 million donors, is run by the World Marrow Donor Association (WMDA). This international database contains the HLA types shared by approximately 70 global registries combined. The HLA types listed in the registries were determined when individuals signed up and swabbed their cheeks or (in some countries) completed a blood test.

Donors in the worldwide registry are designated by a number, so when you join Gift of Life, we are the only ones who know your name, and your personal information is protected – only your registry number, HLA profile, gender at birth, and age are shared with the worldwide registry. 

For those who do not find a donor, organizing a donor drive may help to find that matching person. Searching among peoples of the same ethnic group and race, or whose families originally came from the same geographic area, may help in locating a match. 

Does every patient find a match? 

Unfortunately, not yet. Even though more than 41 million people have already volunteered as stem cell and bone marrow donors, this is a tiny fraction of the world's population of more than 8 billion people, making it difficult to find matches for many patients. 

The situation is most urgent for people among minorities. More donors from every demographic group are urgently needed to join the registry, especially those of sub-Saharan African ancestry and those who are multi-racial.

For patients who do not yet have a match in the registry, Gift of Life Marrow Registry can help the family organize recruitment drives in the hope of finding a matching donor among the community. It is extremely helpful to know about the patient’s ancestry or ethnicity when running these drives, because the best chance of finding a matching donor is among those who share the same genetic heritage. This matching does not necessarily correlate with skin color or surface appearance. As many who take commercial DNA tests learn, a family’s genetic heritage can be more complex and interesting than they were aware of.

How you can help save lives

Join the registry: Anyone 18 to 35 and in general good health may join the registry at no cost. Click here to order a swab kit to be sent to you, complete with instructions and a prepaid return envelope. If you are ever a match for a patient, we’ll call you and you may have that unique and miraculous opportunity to save someone’s life! 

Volunteer: If you would like to help us add new donors to the registry, please contact our Volunteer Network  

Sponsor a swab kit:  Gift of Life does not receive government funding and relies on gifts from people like you to pay for the processing of swab kits.  Click here to sponsor a swab kit, or to give a monthly gift.