The Effect of High-Resolution Donor-Recipient HLA Matching and Mismatching Frequencies On Choosing Donor in Chinese Population for Unrelated Allo-HSCT.

Abstract 4503

The relative importance of various human leukocyte antigen (HLA) loci and the resolution level at which they are matched has not been fully defined for unrelated donor (URDs) transplantation. Hematopoietic stem cell transplantation (HCT) from volunteer URDs may give a chance of cure for patients with malignant hematological diseases. Although donor-recipient HLA matching is associated with better outcomes, many are not able to identify an HLA-A, -B, -C, -DRB1, DQB1 matched URD and are faced with choosing the closest matching among the available donors. The Chinese Marrow Donor Program (CMDP) has completed a retrospective high-resolution HLA typing on sufficient patient-donor pairs to analyze high resolution matching and mismatches probability at specific loci. These data are critical for selecting the best available partially HLA-matched donor for patients undergoing HLA-mismatched URD HCT. We have performed high-resolution typing for HLA-A,-B,-C,-DRB1,-DQB1 by using SBT, SSOP and SSP techniques on 1092 donors and 931 patients from the data base of CMDP. Among 1092 donors, the allele with highest frequency were HLA-A*1101, A*0201, A*2402, A*0207, A*3303, A*0206 and A*3001; HLA-B*4001, B*4601, B*5801, B*1302, B*1501, B*5101and B*1301; HLA-Cw*0102, Cw*0702, Cw*0304, Cw*0801, Cw*0602, Cw*0303, Cw*0302 and Cw*0401; HLA-DRB1*0901, DRB1*1501, DRB1*1202, DRB1*0701, DRB1*0803, DRB1*0405, DRB1*0301 and DRB1*1101; HLA-DQB1*0301, DQB1*0303, DQB1*0601, DQB1*0202, DQB1*0602, DQB1*0302, DQB1*0401, DQB1*0201 and DQB1*0502. The probability of HLA high-resolution DNA matching between 1092 donors and 931 patients(10/10 match) was 16.7%. Mismatching at a single HLA-A, -B, -C, -DRB1 or DQB1 locus (9/10) was 17.7%. A single mismatch at each locus of HLA-A, -Cw,- DRB1,- DQB1,- B was 6.8%, 6.3%, 2.0%, 1.7%, and 0.8%, respectively. Double mismatch (8/10) was 18.4%, such as loci A+ Cw(5.0%), DRB1+DQB1(4.6%) and B+ Cw(3.8%). The donor/patient pairs mismatched between allele of A*0201 and A*0206, A*0201 and A*0207, A*1101 and A*1102, B*4006 and B*4002, B*1501 and B*1527, Cw*0304 and Cw*0302, Cw*0304 and Cw*0303, DRB1*1501 and DRB1*1502, DRB1*1202 and DRB1*1201, DRB1*0406 and DRB1*0403, DRB1*1401 and DRB1*1454, DQB1*0303 and DQB1*0302, respectively, were statistically associated with lower-risk Allo-HSCT. These results suggested that high-resolution DNA matching or mismatching for HLA-A, -B, -C, -DRB1 and DQB1 alleles could be associated with better clinical outcome and higher survival. Furthermore, the identification of high risk mismatch and permissive mismatch would be beneficial for the selection of a suitable donor.