Article Under Review
This article is undergoing editorial and medical review. We regularly update content as part of our commitment to providing patient-centered, accurate, evidence-based information.
Overview
HLA is your immune ID card. Everyone has HLA proteins on the surface of every cell in their body. When your cells go into the patient, their immune system looks at your HLA and decides: is this mine, or is this foreign. The closer your HLA matches theirs, the better the odds of success.
A perfect 10-out-of-10 match is ideal. A 9-out-of-10 is usually acceptable. Match quality affects how much chemotherapy the patient needs before transplant and how well their body accepts your cells without fighting them. You were selected for this patient because your genes are right for them.
How HLA matching works
HLA matching determines transplant success. You have 6 major HLA genes from each parent. Perfect matching (6/6) is rare except between identical twins or siblings. Better matches reduce rejection risk.
HLA basics:
- You inherit one HLA haplotype from each parent
- 6 major HLA loci create millions of possible combinations
- Perfect matches rare in unrelated donors
- Registry expansion improves matching opportunities
- Better matches predict higher survival rates
How HLA matching works
HLA proteins sit on the surface of every cell in your body. Your immune system uses HLA to recognize "self" versus "foreign." When your cells are transplanted into a recipient, their immune system sees your HLA and decides: "Is this mine, or is this foreign?" The closer your HLA matches theirs, the more "self" your cells appear.
You have two sets of HLA genes (one from each parent). Each set includes 6 main genes: HLA-A (two copies), HLA-B (two copies), and HLA-DR (two copies). This creates 6 major HLA loci, and you inherit different versions (alleles) at each locus. You match a recipient if your alleles at these 6 loci match theirs.
Perfect matching (6/6 match) is rare except between identical twins or HLA-identical siblings. In the general population, perfect matching between unrelated people happens by chance—you could search millions of people and never find a 6/6 match.
- You have 6 major HLA genes (plus many others)
- Each gene has two copies (from each parent)
- Matching improves with genetic similarity
- Perfect matches are rare in unrelated donors
- Better matching reduces rejection risk
Match levels
Match quality ranges from perfect to poor. These categories help predict transplant outcomes, though the spectrum is continuous. A 5/6 match performs almost as well as a 6/6 match; a 1/6 match is unlikely to engraft successfully.
Matched related donor (MRD)
Matched related donors are family members with perfect HLA matching. This happens when you inherit the same set of HLA genes from your parents as your sibling or other relative. Siblings have a 25% chance of being perfect matches (inheriting the same HLA genes from both parents), a 50% chance of being "haploidentical" (matching at one HLA haplotype), and a 25% chance of being completely unmatched.
Parents and adult children never perfectly match because they share exactly 50% of their HLA genes (one set inherited from the parent, one from the other parent). However, a parent-child match is often better than unrelated donor matches because of genetic relatedness.
MRD transplants have excellent long-term outcomes. Graft failure rates are low (<5%), and long-term survival is better than other donor types. If you're an MRD match, you're the ideal donor for your relative.
Matched unrelated donor (MUD)
Matched unrelated donors are registry donors matching the patient at 10/10 HLA at high resolution. Despite being unrelated, the genetic match is excellent. MUD transplants perform very well—outcome data shows survival rates approaching or matching MRD outcomes when donors are young and healthy.
Finding a MUD takes time because you're searching millions of potential donors. Patients with common HLA types find matches more easily; patients with rare HLA types might search for months or years. Diversity in registries is crucial because patients are most likely to match someone from their own ancestry.
MUD transplants now account for more than half of unrelated stem cell donations. Improved matching techniques and better supportive care have made MUD outcomes excellent.
Haploidentical donor
Haploidentical donors match the recipient at one HLA haplotype (3/6 loci). Historically, these transplants had high failure rates. Modern techniques, particularly post-transplant cyclophosphamide (PTCy), have dramatically improved outcomes.
Haploidentical characteristics:
- Typically family members with half-HLA match
- Valuable when MUD or MRD options unavailable
- Modern PTCy techniques improve engraftment
- Outcomes increasingly favorable with new approaches
Why matching matters
Perfect HLA matching virtually eliminates the risk of acute graft-versus-host disease (GVHD), where transplanted immune cells attack the recipient's tissues. It also allows successful engraftment with lower doses of chemotherapy and less risk of graft failure (rejection). Patients with perfect matches have fewer complications and better long-term outcomes.
Matching impact:
- Perfect matching eliminates acute GVHD risk
- Better matching reduces transplant complications
- Perfect matching allows reduced chemotherapy
- Better matching predicts long-term survival
- Extremely poor matches fail to engraft
Poorer matching increases GVHD risk, which causes skin rashes, liver damage, and organ damage. For some diseases, mild GVHD is desired (graft-versus-leukemia effect). For diseases where GVHD is harmful, perfect matching is ideal.
- Perfect matching eliminates acute GVHD risk
- Better matching reduces transplant complications
- Perfect matching allows reduced chemotherapy
- Better matching predicts long-term survival
- Extremely poor matches fail to engraft
When you are asked to donate
When you're identified as a potential match, your match quality is communicated to the recipient's transplant center. If you're a 10/10 MUD match, the center might contact you and the patient immediately, because the search can stop. If you're a 9/10 or 8/10 match, the center might continue searching for a perfect match while also offering you as an option.
The selection process:
- Patient transplant teams receive your HLA match information
- Better matches are preferred but don't guarantee selection
- Teams decide whether to use you based on multiple factors
- Match quality motivates rapid response and contact
- Your genes are valuable to this specific patient
Once you're selected, your role becomes active: full evaluation, commitment to collection, and following through. Your match quality—whether perfect or very good—reflects that you're likely to give this patient the best possible outcome.
- Patient teams receive your HLA match information
- Better matches are preferred
- Patient teams decide whether to use you
- Match quality motivates rapid response
- Your genes are valuable to this patient
What if you are not a match?
If you're not a match to a specific patient, you remain in the registry and can match to someone else. You might be matched to a different patient months or years later.
Not matching for family donors:
- You wanted to help your relative but genes don't align
- Genetic mismatch is chance, not your fault
- Families can pursue unrelated donors
- Families can consider alternative treatments
- Multiple siblings may find at least one match
- Emotional investment still matters even if mismatch occurs
Additional Detailed Information
Additional Information
HLA genetics and inheritance
HLA haplotype inheritance. HLA genes are inherited as two haplotypes (sets of inherited alleles). You have one haplotype from each parent. For a 6/6 match, both siblings must inherit the same haplotype from each parent—occurring with 25% probability.
HLA diversity and alleles. Over 20,000 distinct HLA alleles have been identified globally. This diversity reflects human population diversity and ancient evolutionary history. Common HLA types in one ancestry might be rare in another, explaining why ancestry affects match probability.
Linkage disequilibrium. HLA genes are inherited in blocks because they're closely linked on chromosome 6. Knowing someone's HLA-A type provides some information about their likely HLA-B and HLA-DR types. This genetic linkage has historical origins in ancient populations.
Match quality outcome predictions
10/10 MUD outcomes. Five-year overall survival rates for 10/10 MUD transplants approach 60-70% for patients with acute leukemia in remission. Graft failure rates are <3%. Non-relapse mortality is 10-15%.
Haploidentical outcomes. With PTCy-based regimens, five-year survival rates for haploidentical transplants are 50-65%, approaching or meeting MUD outcomes. Graft failure rates are 5-10%. Chronic GVHD incidence is lower than HLA-mismatched unrelated donor transplants, potentially around 30-40%.
MRD outcomes. Five-year survival for MRD transplants is 65-75% for acute leukemia in remission. Graft failure rates are <3%. Non-relapse mortality is lowest among donor types.
High-resolution HLA typing methods
DNA-based typing. Uses DNA sequencing (next-generation sequencing) to determine HLA alleles at single-nucleotide resolution. Can identify rare alleles. High-resolution typing identifies whether matches are truly perfect or differ at the nucleotide level.
Serologic typing. Older method using antibodies recognizing HLA proteins. Less precise than DNA typing. Now primarily used for confirmatory testing or when DNA typing is unavailable.
Registry matching algorithms
NMDP search algorithm. Prioritizes HLA match quality, then considers donor age, fitness, cytomegalovirus (CMV) status, and ABO compatibility. Once a 10/10 match is identified, the search typically stops, though the patient's team might request continued searching if specific donor characteristics are desired.
Written By:
Transplants.org Staff
Last Reviewed: February 26, 2026
Informed By:
Transplants.org, with participation from 23 leading U.S. transplant centers, led the largest comparative analysis of patient educational materials in transplant history. We recognize the participating centers who helped inform and inspire our direction with initial patient-centered educational content:
- Mayo Clinic (Co-Author)
- Vanderbilt University Medical Center (Co-Author)
- Johns Hopkins Hospital (Co-Author)
- UCLA Medical Center (Co-Author)
- UCSF Medical Center (Co-Author)
Transplants.org is an independent nonprofit organization and participation is not an endorsement by these organizations.
