HLA and Stem Cell Transplantation

What is HLA?

HLA stands for “human leukocyte antigen.” These are protein molecules that we inherit from our parents. We currently know about nearly 600 different HLA molecules. Before you have a stem cell transplant, your HLA type must be determined. This is done by taking a blood sample.

The laboratory will also determine the HLA type of anyone who may donate stem cells to you. It is important in stem cell transplants to see how closely the HLA of the transplant patient matches the HLA of the stem cell donor. The HLA “match” is the number of HLA molecules that any two people have in common. HLA matching is usually based on six HLA molecules. The more molecules two people share, the better the match. When two individuals share the same HLA type, they are said to be a good match. That is, their immune systems will not see each other as “foreign” and are less likely to attack each other.

The most likely place to find an HLA match between two people is among siblings (brothers and sisters who have the same mother and same father). If two siblings inherit the very same HLA molecules from both parents, they are said to be an “HLA identical match.”

You have a 25 percent (1 in 4) chance of being an HLA identical match with your sibling. Why? Because there is a basic rule in HLA inheritance: You have a 25 percent chance of inheriting the same HLA molecules as your sibling, a 25 percent chance of inheriting none of the same HLA molecules as your sibling, and a 50 percent chance of inheriting half of the same HLA molecules as your sibling.

However, two unrelated people can just happen to be a good HLA match, too. Although it is less likely, it is possible that you could have some of the same HLA molecules as a friend or as someone you don’t even know. If you and your friend share three HLA molecules, for example, then you are said to be a “three HLA antigen match.”

Stem Cell Transplants

In order to treat certain diseases, it is necessary to give whole body irradiation and high dose chemotherapy. While this therapy destroys malignant cells, unfortunately it also destroys the cells responsible for generating red blood cells, white blood cells and platelets. In order for the patient to survive after radiation and chemotherapy, these cells (called “hematopoietic stem cells”) must be transfused back into the patient. They then migrate to the bone marrow, divide, and eventually produce new blood cells and platelets.

There are three main sources of hematopoietic stem cells. Stem cells that circulate throughout the blood stream are called “peripheral blood stem cells” or PBSCs. Another source is the bone marrow, where most stem cells reside. A third source of stem cells is the umbilical cord of a newborn baby.

If the hematopoietic stem cells transfused into the patient are from another individual, it is best if the cells carry the same HLA molecules as the patient — otherwise, the patient may either reject the stem cell transplant or the transplanted stem cells may react to the patient’s tissues in what is termed “graft-versus-host disease.”

Finding the Best Match

When a doctor decides that a stem cell transplant is the best treatment for a patient, he or she will request a family study. The patient, all of his or her siblings, and usually their parents will have their blood drawn for HLA typing. If one of the family members is an HLA identical match, the lab will do further testing to be absolutely sure that they are the best match possible. This usually involves taking the patient’s and the donor’s DNA from the blood cells and typing the HLA genes to show that they are identical.

If none of the siblings or the parents are a good HLA match, the doctor will sometimes ask to have additional family members tested. These are usually aunts, uncles, cousins and grandparents. If it happens that there are no close HLA matches within the patient’s family,a search will be initiated for an unrelated donor with the same HLA molecules as the patient.

Glossary of HLA Terms

  • HLA: human leukocyte antigen, proteins we inherit from our parents
  • HLA Matching: the number of HLA molecules two people have in common
  • HLA Antibodies: proteins in the patient's blood against the donor's HLA that could attack transplanted or transfused cells
  • PRA: panel reactive antibody, a measure of how much HLA antibody the patient has
  • Stem Cell: cells responsible for generating red blood cells, white blood cells, and platelets
  • Red Blood Cell: the cells that carry oxygen to all parts of the body
  • White Blood Cell: the cells of the immune system that fight off germs
  • Platelets: the cells that form clots to stop bleeding
  • Bone Marrow: the inner spongy portion of large bones, where most stem cells reside
  • Graft-versus-Host Disease: an immune attack by transplanted donor cells against the patient’s body
  • ABO: blood type, a person can be A, B, AB or O blood type