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高分辨率配型在瑞士非亲缘异基因供者干细胞移植中的影响

Impact of high-resolution matching in allogeneic unrelated donor stem cell transplantation in Switzerland.

作者信息

Chalandon Y, Tiercy J-M, Schanz U, Gungor T, Seger R, Halter J, Helg C, Chapuis B, Gratwohl A, Tichelli A, Nicoloso de Faveri G, Roosnek E, Passweg J R

机构信息

Hematology Service, Department of Internal Medicine, University Hospital, Geneva, Switzerland.

出版信息

Bone Marrow Transplant. 2006 May;37(10):909-16. doi: 10.1038/sj.bmt.1705353.

Abstract

It is currently unknown what degree of human leukocyte antigen (HLA)-mismatching is acceptable in unrelated donor hematopoietic stem cell transplantation (UD-HSCT). Mismatches at some loci may be more permissive than others. We have analyzed the effect of high-resolution HLA-matching on outcome of all 214 consecutive recipients of UD-HSCT carried out in Switzerland. All typing was by the Swiss reference laboratory. Donor-recipient pairs were HLA-10/10 matched (n=130) or mismatched for either HLA-A/-B/-DRB1/multiple loci (n=33; (HLA-A/-B=10); (-DRB1=8); (multiple=15)); HLA-C (n=29) or HLA-DQ/-DRB3 (n=22; (DQ=16); (-DRB1=6)). The median follow-up was 32 months. Survival probabilities (+/-95% confidence interval) at 3 years were 57 (+/-10)% for recipients of HLA 10/10-matched transplants, 53 (+/-22)% for recipients of HLA-DQ/-DRB3-mismatched transplants, 44 (+/-20)% for recipients of HLA-C-mismatched transplants and 0% for recipients of transplants mismatched at HLA-A/-B/-DRB1/multiple loci (P<0.0001). In multivariate analyses, HLA compatibility was the variable most significantly associated with survival and treatment-related mortality. We found important differences in survival in recipients of UD-HSCT with best results for transplants from 10/10 matched donors. Single mismatches at HLA-DQ/-DRB3 were well tolerated, mismatches at HLA-C had intermediate results and mismatches at HLA-A/-B/-DRB1/multiple loci resulted in poor survival.

摘要

目前尚不清楚在非亲缘供者造血干细胞移植(UD-HSCT)中,人类白细胞抗原(HLA)错配程度达到何种程度是可以接受的。某些位点的错配可能比其他位点更具耐受性。我们分析了高分辨率HLA配型对瑞士连续进行的214例UD-HSCT受者结局的影响。所有分型均由瑞士参考实验室完成。供者-受者对HLA-10/10配型(n=130),或在HLA-A/-B/-DRB1/多个位点错配(n=33;(HLA-A/-B=10);(-DRB1=8);(多个=15));HLA-C错配(n=29)或HLA-DQ/-DRB3错配(n=22;(DQ=16);(-DRB1=6))。中位随访时间为32个月。3年时的生存概率(±95%置信区间),HLA 10/10配型移植受者为57(±10)%,HLA-DQ/-DRB3错配移植受者为53(±22)%,HLA-C错配移植受者为44(±20)%,HLA-A/-B/-DRB1/多个位点错配移植受者为0%(P<0.0001)。在多变量分析中,HLA相容性是与生存和治疗相关死亡率最显著相关的变量。我们发现UD-HSCT受者的生存存在重要差异,10/10配型供者的移植效果最佳。HLA-DQ/-DRB3的单个错配耐受性良好,HLA-C错配结果中等,HLA-A/-B/-DRB1/多个位点错配导致生存率低。

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