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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 study the distributed characteristics of KIR2DL1 alleles frequencies and the recognition HLA-C ligand in the Chinese Han population. Methods The 111 patients and 116 donors from CMDP were performed the KIR2DL1 high-resolution typing and KIR genotyping using sequence-based testing (SBT) and PCR-SSP methods. Results A total of 224 individuals with KIR2DL1 locus was predominantly observed and accounted for 98.68% (224/227). There were 3 difference KIR2DL1 alleles, include of KIR2DL1 ∗ 00302, ∗ 00201 and ∗ 00401 alleles polymorphism. The most commonly of phenotype frequency were observed KIR2DL1 ∗ 00302(84.82%, 380/448), KIR2DL1 ∗ 00201 (12.05%, 54/448) and KIR2DL1 ∗ 00401 (3.13%, 14/448), present at allele genetype frequencies of 61.04%, 6.22% and 1.58%. The allele homozygotic type of KIR2DL1 ∗ 00302 and KIR2DL1 ∗ 00302 was the most frequency in the six gene complex of KIR2DL1 allele by high resolution typing. The allele heterozygous type of KIR2DL1 ∗ 00302 and KIR2DL1 ∗ 00401 had present statistically significant difference in haplotypes A/A and B/x( P = 0.001), and KIR2DL1 ∗ 00401 was lacked all A/A haplotype. The KIR2DL1 ∗ 00302 and KIR2DL1 ∗ 00201 allele had significant positive associations between different KIR pairs of KIR2DS1,KIR2DS4,KIR2DS5,KIR2DL3 and KIR3DL1/S1 using linkage disequilibrium analysis ( P ⩽ 0.001), respectively. In the receptor-ligand of KIR/HLA model after allo-HSCT, KIR2DL1 ∗ 00302 alleles and their HLA-C2 group ligands had correlation. KIR2DL1 ∗ 00302 and HLA-C ∗ 06:02 was the most common of combination ligand model, but KIR2DL1 ∗ 00302 and HLA-C ∗ 01:02 was the most frequent mismatch ligand model that it could be develop of NK cell-induced alloreactivity, meanwhile there was statistically significant difference of frequency distribution ( P < 0.05). Conclusion The KIR2DL1 ∗ 00302 is the most frequency allele in Chinese Han population. The KIR2DL1 high resolution typing would be beneficial for predicting donor NK cells alloactivity after hematopoietic stem cell transplantation and selecting suitable donors. [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]

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 analyze the association between CYP3A5 single nucleotide polymorphisms (SNPs) and tacrolimus (Tac) or cyclosporine (CsA) level in renal transplant recipients during a 4-year follow-up. Methods 103 renal transplant patients were recruited and assigned into three groups according to their CYP3A5 allele ∗ 3/ ∗ 3, ∗ 1/ ∗ 3, or ∗ 1/ ∗ 1. The concentrations of Tac or CsA at time zero (C0) were measured before the drug administration. And the association between different alleles with Tac or CsA dose-adjusted C0 were further analyzed. Results During the first month after transplantation, recipients with CYP3A5 ∗ 3/ ∗ 3 allele exhibited significantly higher Tac C0 than the recipients with CYP3A5 ∗ 1/ ∗ 1 allele. The Tac dose/day used for recipients with CYP3A5 ∗ 3/ ∗ 3 allele was significantly lower than that for recipients with CYP3A5 ∗ 1/ ∗ 1 or CYP3A5 ∗ 1/ ∗ 3 allele. The Tac C0 of recipients with CYP3A5 ∗ 3/ ∗ 3 allele was significantly difference than that of the recipients with CYP3A5 ∗ 1/ ∗ 3 and CYP3A5 ∗ 1/ ∗ 1 allele at 3 months, 6 months, 12 months, 24 months and 48 months respectively during the 4-year follow-up after transplantation. The trough concentrations/doses of CsA were not associated with the CYP3A5 SNPs. Conclusion Patients with homozygous CYP3A5 ∗ 3/ ∗ 3 allele need less dosage of Tac to maintain a therapeutic concentration after renal transplantation. [ABSTRACT FROM AUTHOR]