What is HLA matching?

HLA stands for Human Leukocyte Antigen. These are proteins on the surface of nearly every cell in your body that act as ID markers — they tell your immune system that a cell belongs to you. Your HLA type is set by your genes, and you inherit half of it from each parent.

In a bone marrow transplant, doctors match the donor’s HLA type to the patient’s so that the donated cells — which become the patient’s new immune system — do not attack the patient’s body, and the patient’s body does not attack the donated cells. A close match is called an HLA-matched donor.

HLA matching is a genetic compatibility test. It is done from a cheek swab or a blood sample. The lab reads specific HLA markers in your DNA and compares them against patients waiting for a donor. The National Cancer Institute describes HLA matching as testing tissue for the antigens that make up a person’s tissue type.

The HLA genes sit on chromosome 6, in a region called the Major Histocompatibility Complex (MHC). Six HLA proteins matter most for transplantation: A, B, C, DR, DQ, and DP. Together they form the profile a transplant team reads when looking for a donor.

You carry two complete sets of these proteins — one inherited from each parent. The HLA type used in matching is that combined profile. Because it is inherited as a set, your full siblings have a 1-in-4 chance of matching you across the board, while an unrelated match is far rarer.

Each HLA gene comes in a large number of variants, called alleles, and the catalogue keeps growing as more are sequenced. The authoritative count is maintained by the IPD-IMGT/HLA database, which lists more than 44,775 HLA alleles as of IPD-IMGT/HLA database release 3.64, 2026. That enormous diversity is exactly why a specific patient’s set of markers can be so hard to match.

Your full HLA profile is shared with some other people, but for any one patient the universe of truly compatible donors is small. This is the core reason registries need millions of members rather than thousands. Fred Hutchinson Cancer Center, where modern bone marrow transplantation was pioneered, explains how this HLA matching underpins the search for an unrelated donor.

For a transplant, HLA matching is usually evaluated at 8 or 10 specific markers. A 10/10 match means all ten agree. An 8/10 match has two mismatches — still potentially usable, but with a higher risk of complications. The National Cancer Institute defines the human leukocyte antigens these markers represent.

HLA types are inherited from your ancestors. Populations that were separated by geography for thousands of years developed different HLA patterns, so a person of European ancestry is more likely to match other people of European ancestry, and the same holds for African, Asian, and mixed ancestry.

The US registry has historically over-represented white European Americans. As a result, a patient of color in the US has a meaningfully lower probability of finding a fully matched donor than a white patient, and patients with mixed ancestry face the longest odds because their profile is rare in any single population.

The gap is real and measurable. Published analyses of the US registry — including a study of HLA match likelihoods in the New England Journal of Medicine (Gragert et al., 2014) and outcomes data from the HRSA C.W. Bill Young Cell Transplantation Program — show white patients finding a fully matched unrelated donor at the highest rate, roughly 75 to 80 percent. The rate is materially lower for patients of color: Black or African American patients face the longest odds, with published estimates around 30 percent or lower, and Hispanic and Asian patients fall in between.

The fix is diversity in the registry. Each new member from an underrepresented community measurably raises the chance that future patients from that community will find a match. That is the scientific reason representation on the registry is a matter of life and death, explained more fully on the donors of color page.

A 10/10 HLA match minimizes the risk of graft-versus-host disease (GVHD), a condition in which the donor’s immune cells, carried in the transplant, attack the recipient’s body. The closer the match, the lower that risk tends to be. GVHD matters because the donated cells go on to become the patient’s new immune system, so the better the HLA markers agree, the less likely those new cells are to treat the patient’s own tissue as foreign.

Even with a perfect HLA match, GVHD can still occur. Matching reduces the risk rather than eliminating it, and modern transplant protocols use medications and conditioning regimens to manage it. Memorial Sloan Kettering Cancer Center describes how its bone marrow and stem cell transplant teams weigh match quality against these risks.

Some transplants use haploidentical matching, where only half the HLA markers match — typically from a parent or child. Advances in transplant protocols have made this increasingly viable, expanding options for patients who cannot find a fully matched donor. Cord blood transplants, which use stem cells from donated umbilical cord blood, require less stringent HLA matching and provide another option, as the Dana-Farber stem cell transplant program explains.