HapLogic

This page provides a high-level overview of HapLogic^SM, our match algorithm designed to help transplant centers identify the best potential human leukocyte antigen (HLA) matches between a patient and donor or cord blood unit (CBU). Further details can be found in Chapter 2 of Transplant Center Manual of Operations.

HapLogic Match Algorithm

Our HapLogic match algorithm identifies donors and CBUs with the highest potential to match each patient. A donor will appear as a potential match if there is at least a 5 of 6 HLA antigen match at HLA-A, -B, and -DRB1. Donors without HLA-DRB1 typing must match at least 4 of 4 antigens at HLA-A and -B to appear as a potential match. A CBU will appear as a potential match if there is at least 4 of 6 antigen match at HLA-A, -B, and -DRB1.

HapLogic has two main components, genotype list matching and haplotype frequency calculations, which together provide useful information about the match potential of the donor or CBU to the patient.

Genotype List Matching

HapLogic determines the match potential between a patient and donors or CBUs. HapLogic does this by creating a list of possible allele combinations, called a genotype list, for each donor typing. This list is compared to the patient’s typing to determine the potential degree of match.

Haplotype Calculations

HapLogic uses population genetics, haplotype frequencies, and mathematical models to predict the likelihood that a donor or CBU will be a high-resolution match with the patient. This program also incorporates race/ethnicity into the calculation. The haplotype calculations are displayed on the search in two ways: 1) summarized by individual percentage at each HLA-A, -B, -C, -DRB1, and -DQB1 locus and 2) as a composite percentage of HLA-A, -B, -C, -DRB1, and -DQB1.

Match Category

Donors are grouped based on both allele and antigen level matching at HLA-A, -B, -C, -DRB1, and -DQB1. These groupings are referred to as “Match Category.” Match categories classify donors and CBUs in the category of their highest potential match, based on the presence of mismatches. Donors, potentially high resolution, with no known mismatches have a match category of “10/10,” while donors with one known mismatch are in the “9/10” match category, etc.

CBUs are grouped based on their antigen level matching at HLA-A and -B, but are grouped based on high-resolution (both an allele and antigen) match at HLA-DRB1 when considering the x/6 traditional match category. CBUs are also listed based on allele and antigen level matching at HLA-A, -B, -C, and DRB1 (x/8).

Match Grades

HapLogic compares the HLA typing of patients and donors or CBUs at each locus and assigns a match grade (if typing results are available) for each allele at HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1. There are currently four match grade symbols identified as follows:

“A” Patient and donor or CBU are typed by DNA and are allele matched
"P” Patient and donor or CBU are typed by DNA or serology and are a potential allele match. Note: Blank serology at HLA-C is considered a potential match for patients with DNA defined C typing
“L” Patient and donor or CBU are typed by DNA and are allele mismatched
“M” Patient and donor or CBU are typed by DNA or serology and are an antigen level mismatch

Donor/Cord Sort

After HapLogic performs the genotype list matching, assigns match grade and match category and calculates probabilities, the donors and CBUs are listed on the search report.
Potential donors are prioritized in the following default order:

Match category x10 or x/8 (default search is based on x/8 matching)
Probability calculation in descending probability buckets (85-99%, 45-84%, 11-44%; all donors with a 0-10% chance of matching in a category are sorted where they first have a >10% chance of matching)

For x/10 (10/10, 8/8, 9/10, 7/8, 8/10, 6/8, etc.)

For x/8 (8/8, 7/8, 6/8, 5/8, 4/8)

Donor age (30 and under, 31-39, 40-49, 50+)
U.S. based/non-U.S. based donors + Donor Readiness Score (DRS)

U.S. based: DRS 71% and higher

U.S. based: DRS 61-70%

U.S. based: DRS 46-60%

U.S. based: DRS 36-45%

U.S. based: DRS 35% and lower + N/A, non-U.S. based: DRS 71% and higher

Non-U.S. based: DRS 61-70%

Non-U.S. based: DRS 51-60%

Non-U.S. based: DRS 31-50%

Non-U.S. based: DRS 30% and lower + N/A

DPB1 TCE

Match and Permissive

Potential

Untyped DPB1 with a TCE Prediction 51% and higher

Untyped DPB1 with a TCE Prediction 50% and lower

Non-Permissive

Integer age
Donor status

Potential CBUs are prioritized in the following order:

Match category (antigen level match at HLA-A and -B; allele and antigen match at HLA-DRB1)
TNC (highest to lowest)
CD34 (highest to lowest)

The sorts can be changed and saved per user preferences. See MatchSource Interactive Training Guide for more information on how to manage lists.

HapLogic does not take non-HLA factors such as sex, blood type, CMV status, etc., into consideration in the donor sort.

References

Spellman S, Setterholm M, Maiers M, et al. Advances in the selection of HLA-compatible donors: Refinements in HLA typing and matching over the first 20 years of the National Marrow Donor Program registry. Biol Blood Marrow Transplant. 2008; 14(9; Suppl. 3): 37-44.
Holdsworth R, Hurley CK, Marsh SGE, et al. The HLA dictionary 2008: A summary of HLA- A,-B, -C, -DRB1/3/4/5, and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR, and -DQ antigens. Tissue Antigens. 2009; 73(2): 95-170.
Hurley CK. DNA Methods for HLA Typing: A Workbook for Beginners; Version 7. Washington, D.C.: Georgetown University School of Medicine; 2008.
Hurley CK, Setterholm M, Lau M, et al. Hematopoietic stem cell donor registry strategies for assigning search determinants and matching relationships. Bone Marrow Transplant. 2004; 33(4): 443-450.
Dehn, J., et al., HapLogic: A Predictive Human Leukocyte Antigen-Matching Algorithm to Enhance Rapid Identification of the Optimal Unrelated Hematopoietic Stem Cell Sources for Transplantation. Biol Blood Marrow Transplant, 2016. 22(11): p. 2038-2046.