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HLA-A/B/C/DRB1/DQB1 常见单体型对无关造血干细胞移植供者选择结果的影响。

Contribution of HLA-A/B/C/DRB1/DQB1 common haplotypes to donor search outcome in unrelated hematopoietic stem cell transplantation.

机构信息

Laboratory of Immunology, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris, University Paris VII, 48 Boulevard Sérurier, Paris Cedex 19, France.

出版信息

Biol Blood Marrow Transplant. 2011 Nov;17(11):1612-8. doi: 10.1016/j.bbmt.2011.03.009. Epub 2011 Apr 12.

DOI:10.1016/j.bbmt.2011.03.009
PMID:21536142
Abstract

In unrelated hematopoietic stem cell transplantation (HSCT), the prediction of donor search outcome at the time of search initiation is of great value for the physicians to delineate the strategy of patient care. The probability of finding an unrelated donor is high for patients who carry at least 1 of the 10 most common HLA haplotypes in Caucasians. As only 10% to 20% patients respond to this criterion, here we aimed at finding additional common haplotypes to improve the prediction of a successful search. HLA broad HLA-A/B/DRB1 haplotypes that were observed with frequencies ≥0.19% in patient families of European origin and that split into ≤2 predominant 4-digit HLA-A/B/C/DRB1/DQB1 haplotypes were considered as common. Carriage of at least 1 of those in 168 patients of various geographic areas with no family donor was confronted to the chance of finding ≥9/10 HLA-matched unrelated donors. Fifty common 4-digit haplotypes were identified. A higher (P < 5 × 10(-6)) chance of finding a suitable donor was found for 55 of 170 (32%) recipients that carried at least 1 of these common haplotypes. Up to now, estimates classified patients into ≥3 groups of probability with ≥1 intermediate group of poor utility for the clinicians. Considering carriage of these common haplotypes together with the frequencies of alleles and of B/C and DRB1/DQB1 associations, which are carried by patient HLA haplotypes, we could classify the patients into 2 groups of probability with a 98% and 26% chance of finding a donor, respectively. Prediction of search outcome could be improved by including the 50 most common HLA haplotypes in the current approaches.

摘要

在无关造血干细胞移植(HSCT)中,在开始寻找供体时预测供体搜索结果对医生来说具有重要价值,可用于划定患者治疗策略。在高加索人群中,至少携带 10 个最常见 HLA 单倍型之一的患者找到无关供体的概率很高。由于只有 10%到 20%的患者符合此标准,因此我们旨在寻找其他常见单倍型以提高搜索成功率的预测。在具有欧洲血统的患者家庭中观察到频率≥0.19%的 HLA 广泛 HLA-A/B/DRB1 单倍型,并且分为≤2 个主要的 4 位数字 HLA-A/B/C/DRB1/DQB1 单倍型,被认为是常见的。在来自不同地理区域且无家族供体的 168 名患者中,携带至少 1 种这些单倍型的患者与找到≥9/10 HLA 匹配的无关供体的机会进行了比较。确定了 50 种常见的 4 位数字单倍型。携带这些常见单倍型的 170 名(32%)受者中,有 55 名(32%)找到合适供体的机会更高(P<5×10(-6))。到目前为止,这些估计值将患者分为≥3 个概率组,其中 1 个中间组对临床医生的实用性较差。考虑到这些常见单倍型的携带情况以及患者 HLA 单倍型携带的等位基因频率和 B/C 和 DRB1/DQB1 关联频率,我们可以将患者分为 2 个概率组,找到供体的机会分别为 98%和 26%。通过在当前方法中包含 50 个最常见的 HLA 单倍型,可以提高搜索结果的预测。

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