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Abstract: Human leukocyte antigen (HLA), which is extremely polymorphic, plays an important role in stem cell transplantation. The Chinese Han comprise a large population of approximately 1.3 billion with diverse HLA alleles that need to be characterized. Data from 3,296 independent, unrelated Chinese Han individuals (1,457 recipients and 1,839 donors) were provided by the China Marrow Donor Program (CMDP) for donor–recipient confirmatory typing. Sequence-based typing, sequence-specific oligonucleotide probe (SSOP)/High Definition-SSOP, and sequence-specific primer methods were used to obtain 4-digit alleles. A total of 49, 86, 50, 63, and 24 HLA-A, -B, -C, -DRB1, and -DQB1 alleles were observed. Following American Society for Histocompatibility and Immunogenetics (ASHI) common and well-documented (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 are 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. 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 allele list. [Copyright &y& Elsevier]

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 To investigate the impact of patients with anti-HLA antibodies or with donors mismatched at HLA-DP locus on outcomes after unrelated-donor hematopoietic stem cell transplantation (HSCT). Method We explored the data from 123 patients that received allo-HSCT matched for HLA-A, B, C, DRB1, DQB1, and DQA1 (12/12) from unrelated donors from the CMDP with a 2-year follow up. The examination of anti-HLA antibodies was scheduled at 3 time points: before the start of conditioning treatment and 1 month, 3 months after transplantation. Results The presence of anti-HLA antibodies detected before and 1 month, 3 months after transplantation was 37.4% (46/123), 40.2% (47/117), 22.6% (24/106), respectively. 16.4% (18/110) recipients with donors matched in HLA-DPA1 and HLA -DPB1 loci, and the mismatched rate was 83.6% (92/110). Patients with preformed anti-HLA antibodies had delayed platelet recovery. Anti-HLA antibodies detected before and after transplantation were responsible for increased occurrence of grade 2–4 acute graft-versus host disease (aGVHD) and reduced overall survival (OS), especially in acute myeloid leukemia and myelodysplastic syndrome patients. Pre-existing HLA-Ab was an independent risk factor for the GVHD and OS. Unfortunately, we found that HLA-DP mismatches have nothing to do with outcomes after transplantation. For HLA-Ab negative group, HLA-DP matched subgroup had a modest trend towards a lower rate of aGVHD, and a higher occurrence of OS and DFS compared with HLA-DP mismatched subgroup. Conclusions Our results suggest that anti-HLA antibodies detected before and after transplantation had a negative effect of outcomes, but HLA-DP loci mismatches have no significance after HLA- 12/12 matched unrelated donor of allo-HSCT. Anti-HLA antibodies should be the primary consideration in the setting of HLA 12/12-matched unrelated-donor HSCT, followed by the status of HLA-DP matching. [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]

Abstract: Killer cell immunoglobulinlike receptors (KIRs) are a diverse family of receptors on natural killer cells. The KIR2DS4-deleted variant differs from the normal KIR2DS4 sequence by a 22-bp deletion in exon 5, which causes a frame shift, yielding a truncated KIR2DS4 protein with loss of the transmembrane and cytoplasmic domains of the full-length KIR2DS4 protein. A sequence-based testing and TOPO TA cloning system identifying and distinguishing alleles of the KIR2DS4 gene was established. The method was applied to 150 Chinese Han individuals: 75 patients who received T-depleted hematopoietic stem cells transplantation and their unrelated donors, establishing frequencies of 2DS4 allele and KIR gene within the local population. A majority (139) of the 150 samples (92.7%) were positive for KIR2DS4. The ratio of deleted to nondeleted versions of KIR2DS4 was approximately 1:2. Three KIR2DS4 novel alleles were identified. Forty-four percent individuals carried two group A haplotypes. The 17 KIR gene loci were found in 21.3%–100% in the population. Our findings suggest that the Chinese Han population is distinct in KIR gene frequencies and 2DS4 allele frequencies in comparison with some other populations. [Copyright &y& Elsevier]

Aim To investigate the impact of donor Killer Immunoglobulin-like Receptors (KIR) genotypes and centromeric motif B (Cen-B) on clinical outcomes after unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) for Chinese population. Method A total of 210 Chinese patients underwent URD-HSCT were investigated in this 4-year retrospective study. KIR genotyping and HLA typing were performed for the population. Results The risk of transplant from Bx1 donors and the benefit of the presence of Cen-B (ignoring the number) were observed for standard risk AML/MDS patients Donor KIR genotype Bx was associated with significant improved OS (P = .026) and RFS (P = .021), and reduced NRM (P = .017) for AML/MDS patients. A much worse survival was observed for transplants from Bx1donors compared to Bx2, Bx3, and Bx4 donors for patients in CR1, ( n = 82; OS: P = .024; RFS: P = .021). Transplant form donors with Cen-B improved OS (HR = .256; 95% CI = .084 to .774; P = .016) and RFS (HR = .252; 95% CI = .084 to .758; P = .014) for AML/MDS patients in CR1. However, the effect did not increase with the number of Cen-B motifs (cB/B vs. cA/B; OS: P = .755; RFS: P = .768). No effect was observed for high risk AML/MDS and ALL/NHL, CML patients. Conclusions Avoiding the selection of HSCT donors with KIR genotype Bx1 is strongly advisable for AML/MDS patients of standard risk. The presence of cen-B motif rather than the number was more important in donor selection for Chinese population. [ABSTRACT FROM AUTHOR]