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To analyse the effect of HLA‐DPA1 and HLA‐DPB1 allelic mismatches on the outcomes of unrelated donor haematopoietic stem cell transplantation (URD‐HSCT), we collected 258 recipients with haematological disease who underwent HLA‐10/10 matched URD‐HSCT. HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1, ‐DRB3/4/5, ‐DQA1, ‐DPA1 and ‐DPB1 typing was performed for the donors and recipients using next‐generation sequencing (NGS) technology. After excluding 8 cases with DQA1 or DRB3/4/5 mismatches, we included 250 cases with HLA‐14/14 matching for further analysis. Our results showed that the proportion of matched DPA1 and DPB1 alleles was only 10.4% (26/250). The remaining 89.6% of donors and recipients demonstrated DPA1 or DPB1 mismatch. In the DPA1 matched and DPB1 mismatched group, accounting for 18.8% (47/250) of the cohort, DPB1*02:01/DPB1*03:01 allelic mismatches were associated with decreased 2‐year OS and increased NRM. DPB1*02:02/DPB1*05:01 and DPB1*02:01/DPB1*05:01 mismatches showed no impact on outcomes. Moreover, the specific allelic mismatches observed were consistent with the DPB1 T‐cell epitope (TCE) classification as permissive and non‐permissive. We innovatively established an analysis method for DPA1 ~ DPB1 linkage mismatch for cases with both DPA1 and DPB1 mismatched, accounting for 70% (175/250) of the total. DPA1*02:02 ~ DPB1*05:01/DPA1*02:01 ~ DPB1*17:01 linkage mismatches were associated with lower 2‐year OS, especially among AML/MDS recipients. DPA1*02:02 ~ DPB1*05:01/DPA1*01:03 ~ DPB1*02:01 linkage mismatches showed no impact on outcomes. In conclusion, applying the DPA1 ~ DPB1 linkage mismatch analysis approach can identify different types of mismatches affecting transplant outcomes and provide valuable insight for selecting optimal donors for AML/MDS and ALL recipients. [ABSTRACT FROM AUTHOR]

Aim To analyze allele mismatches of HLA-A, -B, -C, -DRB1, -DQB1 and haplotype mismatch of donor-recipient pairs on the outcome of haploidentical transplantation combined with a third part cord blood unit. Methods 230 pairs of donor-recipient were performed HLA-A, B, C, DRB1, DQB1 typing using SBT and SSOP methods from January 2012 to December 2014. Results Pairs were divided into HLA-5/10, 6/10, 7/10 and ⩾8/10 groups according to HLA-A, B, C,DRB1 and DQB1 high resolution typing and matched degrees, the 3-year probability of overall survival (OS) for each group were 48.7%, 59.3%, 71.1%, 38.3%( P = 0.068) respectively. HLA>6/10 matched group associated with significant favorable effect on OS compared with HLA-5/10 matched one ( P = 0.041).When the HLA class I antigen matched on the recipient and donor, improved OS and event free survival (EFS) in HLA-6/10 matched group than in HLA-5/10 matched one ( P = 0.017, P = 0.088), especially in single HLA-A loci allele matched one ( P = 0.013, P = 0.013), were observed. As to the third part cord blood unit, sharing the same haplotype with the recipient-donor pairs produced better platelet recovery than the misfit one (95.3% vs 86.2%, P = 0.007), similar result was found in terms of neutrophil recovery (98.8% vs 96.1%, P = 0.022). Conclusions HLA locus mismatch and haplotype mismatch of the donor and recipient should be useful for selection of the most optimum donor. Co-infused of an unrelated cord blood unit sharing the same haplotype with the recipient-donor pairs could improve hematopoietic recovery. [ABSTRACT FROM AUTHOR]

Aim: Human Leukocyte Antigens (HLA), which is extremely polymorphic, plays an important role in stem cell transplantation. The Chinese Han comprise a large population of approximate 1.3 billion with diverse HLA alleles need to be characterized. Methods: Data from 3296 independent, unrelated Chinese Han individuals (1457 recipients and 1839 donors) were provided by China Marrow Donor Program (CMDP) for donor-recipient confirmatory typing. SBT, SSOP/HD-SSOP and SSP methods were used to obtain 4-digit alleles. Results: A total of 49, 86, 50, 63 and 24 HLA-A, B, C, DRB1, and DQB1 alleles were observed. Following ASHI CWD criteria, CWD alleles for Chinese Han in our laboratory test and other laboratory reports do not quite correlate with the ASHI CWD alleles: A∗11:53, A∗02:34, A∗02:53N, B∗27:24, B∗46:02, B∗55:12, C∗01:06, C∗03:17, C∗06:06, C∗07:66, C∗07:67, C∗08:22, DRB1∗12:10, DQB1∗03:13 and DQB1∗06:05 are CWD, but are not included in the ASHI CWD list. A series of alleles are Well-Documented alleles and listed in the ASHI CWD list. Conversely, A∗26:03, B∗51:03, C∗12:05, C∗15:09, C∗15:11, C∗17:03, DRB1∗11:07, DRB1∗11:11, DRB1∗13:05, DRB1∗13:13, DRB1∗14:06, DRB1∗14:12, DRB1∗14:22, DRB1∗14:25 and DQB1∗06:11 are rare alleles, but are included in the ASHI CWD list. Conclusions: HLA Ethnic diversity is the main reason for the differences in HLA alleles worldwide. The ASHI HLA CWD alleles help reduce the workload and expenses in high-resolution donor registries and the HLA allele frequencies provide a basis from which to predict the chances of finding HLA matching donors. Our data will be meaningful for the CMDP, for other worldwide donor registries, and for an updated ASHI CWD alleles list. [Copyright &y& Elsevier]

Aim: To study the various HLA high resolution typing mismatching of donor-recipient pairs impact to success of unrelated donor hematopoietic stem cell transplantation. Methods: 835 donor-recipient pairs of CMDP data were analyzed from 2005 to 2010. HLA-A, B, C, DRB1 and DQB1 typing were performed using SBT, SSOP and SSP. All the patients were undergoed transplantation for AML (n=288), ALL (n=227), CML (n=187), MDS (n=52), NHL (n=25) and AA (n=42). In the 835 donor-recipient pairs, 362 pairs were completely matched, 473 pairs were mismatched include of single allele and antigen, both allele and antigen, double allele and antigen, multiple allele and antigen. Results: HLA-matched pairs was associated with better overall survival compared with HLA-mismatched pairs (79.83% vs 73.15%), but there were no statistically significant differences. HLA mismatches of single allele plus single antigen were a significant risk factor for OS, DFS and TRM. In the patients of difference FAB groups, OS from high to low in turn was MA, AA, CML, MDS, AML, NHL, ALL. OS of HLA locus mismatching were DRB1(94.4%), DQB1(83.3%), B(75%), A(74.4%) and C(71.4%), respectively. OS of single allele mismatch at HLA locus from high to low in turn was DRB1, C, A, B and DQB1.HLA-A, B, C locus mismatch was statistically significant differences associated with lower OS and gradeII-IVacute GVHD compared with HLA-matched pairs. The donor-recipient pairs with HLA-B∗15:01/B∗15:05, DRB1∗12:01/DRB1∗12:02, C∗04:01/C∗03:04, DQB1∗03:02/DQB1∗03:03 alleles mismatch were priority accepted. But the donor-recipient pairs with HLA-B∗39:01/B∗39:05,C∗15:02/C∗14:02, C∗08:01/C∗03:04,C∗07:02/C∗15:02 alleles mismatch, were nonpermissive. These were risk factors to impact OS and the occurrence of severe aGVHD of HSCT. Conclusions: The high resolution typing for HLA-A, B, C, DRB1,DQB1 can be identified nonpermissive mismatch, that is would be beneficial for the selection of a suitable donor and can be improved higher rates of survival on unrelated donor HSCT. [Copyright &y& Elsevier]

Currently, there is no well-accepted rating system for reliably predicting which HLA-mismatched (MM) unrelated donor should be selected for a patient without an HLA allele-matched donor. We evaluated the ability of an MM ranking system, HistoCheck, to predict the risk associated with HLA class I disparity in a population of 744 single allele or antigen HLA-A, -B, or -C MM myeloablative unrelated donor hematopoietic stem cell transplantation recipients with acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome, facilitated through the National Marrow Donor Program between 1988 and 2003. Multivariate models were used to adjust for other significant clinical risk factors. HLA MMs were scored using the HistoCheck Web-based tool, and the patients were divided into 4 quartiles: dissimilarity score (DSS) 1.04-2.84 (allele MM), DSS >2.84-13.75 (allele and antigen MM), DSS >13.75-19.39 (antigen MM), and DSS >19.39-36.62 (antigen MM). Using the lowest scoring quartile as the reference, the DSS groups were evaluated for associations with relapse, treatment-related mortality, acute and chronic graft-versus-host disease, leukemia-free survival, and overall survival in the entire cohort and also in subset analyses by disease and disease stage. No significant associations were found between DSS and any outcomes in the overall cohort using the quartile categories or treating DSS as a continuous variable. Higher DSS scores were associated with decreased engraftment in early-stage disease (P = .0003), but not in other disease stages. In summary, DSS does not correlate with transplantation outcomes, and the HistoCheck scoring system does not provide an effective technique for ranking HLA class I MM. The dataset used in this study is available to evaluate new algorithms proposed for donor selection. [Copyright &y& Elsevier]