HLA Tissue Typing
Identifying hematopoietic cells that best match the patient’s human leukocyte antigen (HLA) tissue type is one critical factor affecting patient outcomes. Other factors include the patient’s age, co-morbidities, disease, disease stage and transplant timing.
HLA are proteins used by the immune system to recognize the cells that belong in a patient’s body and those that do not.
The first step in identifying matched hematopoietic cells is HLA tissue typing the patient and the patient’s immediate family to assess the possibility of a related donor. For 7 out of 10 patients, a family member will be unable to donate. These patients will need a closely matched unrelated donor or cord blood unit.
Importance of a close match
A high degree of HLA matching between the patient and donor:
- Improves patient survival [1]
- Reduces graft-versus-host disease (GVHD), a post-transplant side effect [2]
- Promotes engraftment (donated cells regenerate new blood-forming cells quicker)[3]
Tissue typing patients To develop an effective donor search strategy, the patient is tissue typed at high resolution to identify the patient's HLA antigens.
- Current data show significantly better post-transplant survival rates when patients and unrelated donors are matched at a high resolution. [4]
- Tissue typing patients at high resolution:
- Enables the HLA expert to find the best matched donor or cord blood unit
- Can reduce total search time and costs because the search strategy is based on complete information.
Certain antigens are important to patient outcomes for hematopoietic cell transplantation. To develop an effective search strategy for an unrelated donor or cord blood unit, patients should be tested at high resolution for 8 antigens, two at each of these locations (loci):
- HLA-A
- HLA-B
- HLA-C
- HLA-DRB1
A search strategy may require additional testing at DRB3, DRB4, DRB5, and DQB1. A transplant center’s protocol may also require more testing.
Identifying patient haplotypes & HapLogicKnowing a patient’s haplotypes can help a transplant physician identify—more quickly and efficiently—the best matched donor or cord blood unit for the patient.
Haplotypes are inherited groups of antigens and alleles
A haplotype is the set of antigens and alleles that tend to be inherited together. Each antigen has what is called an allele. Although two people may have the same antigens, the allele of an antigen may be different.
A person inherits a haplotype from each parent. Some alleles and haplotypes:
- Are more common than others
- Are distributed at different frequencies in different racial and ethnic groups
Every search of the NMDP Registry uses HapLogic
Because antigens and alleles are inherited, some alleles are more likely to be found among a particular ethnicity. [5] These principles are incorporated into HapLogicSM, a matching algorithm developed by the National Marrow Donor Program (NMDP). When searching for a potential donor or cord blood unit through the NMDP Registry, the scientific approach of HapLogic:
- Identifies the donors or cord blood units with the highest potential to match the patient.
- Is used with every search of the NMDP, preliminary or formal
Matching an unrelated donor or cord blood unitMatching refers to the number of antigens that are the same for the patient and donor.
Figure 1. HLA Matching of Patient and Donor
On the left side of Figure 1, the donor matches the patient at all 6 antigens (a 6 of 6 match). On the right side, one of the donor's A antigens does not match the patient's (a 5 of 6 match).
Depending upon the transplant center’s protocol and the patient’s HLA type, the HLA expert (from either the transplant center or the NMDP) may be searching to match 6, 8 or more antigens.
- The NMDP recommends 8 of 8 matching at high resolution for HLA-A, B, C and DRB1.
- An NMDP minimum requirement for a donor is a 5 of 6 match at HLA-A, B and DRB1. For a cord blood unit, the minimum match is 4 of 6.
- Most transplant centers have additional matching requirements.
Several studies have shown that a large cell dose (the number of hematopoietic cells in a cord blood unit) is also important. [6,7,8,9] The cell dose, in relation to the patient's weight, may require more than one cord blood unit for transplant.
More information:
Advances in HLA Typing (marrow.org)
Searching the NMDP RegistryA search conducted through the NMDP Registry includes more than 11 million potential donors and cord blood units around the world.
- A preliminary search lists potential donors and cord blood units that may match the patient.
The potential matches of a preliminary search are often tissue typed at low resolution. This allows the greatest number of donors to be added to the NMDP Registry for the least amount of money. The more potential donors and cord blood units on the NMDP Registry, the greater the possibility of identifying a match for a particular patient.
- A formal search is begun when the patient is referred to a transplant center and additional HLA testing is performed on potential donors or cord blood units. During the formal search, intermediate and high resolution is needed to ensure the best match for the patient.
More information:
Steps: Searching for unrelated hematopoietic cells
References1. Hurley CK, Baxter Lowe LA, Logan B, et al. National Marrow Donor Program HLA-matching guidelines for unrelated marrow transplants. Biol Blood Marrow Transplant. 2003; 9(10):610-615.
http://www.bbmt.org/article/PIIS108387910300329X/fulltext
2. Morishima Y, Sasazuki T, Inoko H. The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood. 2002; 99(11):4200-4206.
http://www.bloodjournal.org/cgi/content/full/99/11/4200
3. Petersdorf EW, Hansen JA, Martin PJ. Major-histocompatibility-complex class I alleles and antigens in hematopoietic-cell transplantation. N Engl J Med. 2001; 345(25):1794-1800.
http://content.nejm.org/cgi/content/abstract/345/25/1794
4. Flomenberg N, Baxter-Lowe LA, Confer D, et al. Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood. 2004; 104(7):1923-1930.
5. Hurley C, Baxter-Lowe LA, Logan B, et al. National Marrow Donor Program HLA-matching guidelines for unrelated marrow transplants. Biol Blood Marrow Transplant. 2003; 9(10):610-615. http://www.bbmt.org/article/PIIS108387910300329X/fulltext
6. Jacobsohn DA, Hewlett B, Ranalli M, et al. Outcomes of unrelated cord blood transplants and allogeneic-related hematopoietic stem cell transplants in children with high-risk acute lymphocytic leukemia. Bone Marrow Transplant. 2004; 34(10):901-907. http://www.nature.com/bmt/journal/v34/n10/abs/1704681a.html
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