[The impact of HLA haplotype and alleles mismatches of donor-recipient pairs on outcome of haploidentical hematopoietic stem cell transplantation with a third part cord blood unit]

Zhonghua Xue Ye Xue Za Zhi. 2016 Jul;37(7):591-6. doi: 10.3760/cma.j.issn.0253-2727.2016.07.010.
[Article in Chinese]

Abstract

Objective: 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 and DRB1 highresolution 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.

目的: 在HLA-A、-B、-C、-DRB1、-DQB1高分辨基因分型的基础上,分析供受者单倍型和等位基因错配在单倍体联合第三方脐血移植对预后的影响。

方法: 回顾性分析2012年1月至2014年12月期间行单倍体联合第三方脐血移植的230例恶性血液病患者,采用基因测序和寡核苷酸探针杂交方法进行供受者HLA-A、-B、-C、-DRB1、-DQB1高分辨基因分型。

结果: 供受者根据HLA-A、-B、-C、-DRB1、-DQB1基因分型结果及相合度,分为HLA-5/10、-6/10、-7/10、≥8/10四组,其3年总生存(OS)率分别为48.7%、59.3%、71.1%、38.3%(P=0.068)。供受者HLA-6/10相合组与HLA-5/10相合组相比,3年OS率差异有统计学意义(P=0.041)。在供受者HLA-6/10相合组:当HLA-Ⅰ类位点(HLA-A、-B、-C)相合3年OS率为61.5%,与HLA-5/10相合组相比差异有统计学意义(P=0.017),且HLA-A位点等位基因相合3年OS及无事件生存(EFS)率分别为90.5%和84.4%,明显高于HLA-5/10相合组(P= 0.013,P=0.013)。供受者与脐血单倍型相合88例,不合51例,两者巨核系重建累积发生率分别为95.3%和86.2%(P=0.007),粒系重建累积发生率分别为98.8%和96.1%(P=0.022)。

结论: 在单倍体联合第三方脐血移植的供者选择中,HLA相合度及等位基因错配对预后均有意义,选择与供受者单倍型相合的第三方脐血可促进移植后造血重建。

MeSH terms

  • Alleles*
  • Fetal Blood / transplantation*
  • Haplotypes*
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Testing
  • Humans
  • Tissue Donors
  • Transplant Recipients

Substances

  • Histocompatibility Antigens Class I

Grants and funding

基金项目:国家自然科学基金(81273226、81072435);江苏省医学创新团队与领军人才(LJ201138);江苏省临床医学科技专项(BL2014038、BL2013013);血液学协同创新中心和优势学科;江苏省普通高校研究生科研创新计划(KYLX_1257)