Institute for Transfusion Medicine, University Hospital, University Medicine Essen, Germany.
Institute for Transfusion Medicine, University Hospital, University Medicine Essen, Germany.
Transpl Immunol. 2024 Feb;82:101985. doi: 10.1016/j.trim.2024.101985. Epub 2024 Jan 4.
Currently, approximately 19 million people with a migration background live in Germany. The majority of those descend from regions where the population has a genetically different distribution of HLA antigens when compared to the HLA frequencies usually found in North Western Europe. In case of severe haematological disorders of these individuals, allogeneic stem cell transplantation may be the treatment of choice. However, finding appropriate histocompatible hematopoietic stem cell donors continues to be a major challenge. If no matching sibling donors are available, there are only few suitable donors with a similar genetic background available in international blood stem cell donor registries. The "BluStar.NRW" project aimed to recruit new blood and hematopoietic stem cell donors with a migration background and to noticeably increase the number of suitable donors for patients within this group. Since December 2017, a total number of 9100 blood and stem cell donors with a migration background were recruited and typed for this project. HLA typing for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 was performed by Next Generation Sequencing. We assessed the proportion of rare alleles according to HLA frequency tables, as defined by a frequency of <1:1000. The rare HLA allele frequencies according to HLA frequency tables of the BluStar.NRW cohort were compared with a matched control donor cohort: Rare HLA-A, -B, -C, -DRB1 and -DQB1 alleles occurred three times more frequent than in the control group, but rare HLA-DPB1 alleles occurred more frequently in the control cohort. This difference was highly significant for all HLA alleles (p < 0.0001 for HLA-A, -B, -C, -DRB1, -DPB1; p = 0.0002 for HLA-DQB1). In addition, the distribution of rare alleles differed between the two groups. To date, 29 work-ups were initiated, 12 PBSC, one BM and three DLI were collected so far out of the BluStar.NRW cohort. The apheresis probability is twofold higher (0.18% vs. 0.07%) compared to the control group which clearly shows a serious medical need. However, 13 work-ups were cancelled in the BluStar.NRW donor cohort which represents an almost twice as higher cancellation rate (45% vs. 25%). This single registry analysis with a large sample cohort clearly indicates that hematopoietic stem cell donors with a migration background represent an adequate donor pool to serve patients of comparable ethnicity.
目前,约有 1900 万移民背景的人居住在德国。这些人中的大多数来自人群 HLA 抗原的遗传分布与北欧西通常发现的 HLA 频率不同的地区。对于这些个体的严重血液疾病,同种异体干细胞移植可能是首选治疗方法。然而,寻找合适的组织相容性造血干细胞供者仍然是一个主要挑战。如果没有匹配的兄弟姐妹供者,在国际血液干细胞供者登记处也只有少数具有相似遗传背景的合适供者。“BluStar.NRW”项目旨在招募具有移民背景的新的血液和造血干细胞供者,并显著增加该组患者的合适供者数量。自 2017 年 12 月以来,共招募并为该项目对 9100 名具有移民背景的血液和干细胞供者进行了分型。通过下一代测序对 HLA-A、-B、-C、-DRB1、-DQB1 和-DPB1 进行 HLA 分型。我们根据 HLA 频率表评估了罕见等位基因的比例,该频率表定义为频率<1:1000。BluStar.NRW 队列的罕见 HLA 等位基因频率与匹配的对照供者队列进行了比较:罕见 HLA-A、-B、-C、-DRB1 和-DQB1 等位基因的发生频率比对照组高三倍,但罕见 HLA-DPB1 等位基因在对照组中更常见。所有 HLA 等位基因的差异均具有统计学意义(HLA-A、-B、-C、-DRB1、-DPB1:p<0.0001;HLA-DQB1:p=0.0002)。此外,两组之间的罕见等位基因分布不同。迄今为止,已经启动了 29 项工作,从 BluStar.NRW 队列中收集了 12 份 PBSC、1 份 BM 和 3 份 DLI。与对照组相比,单次采集的概率高出一倍(0.18%比 0.07%),这清楚地表明存在严重的医疗需求。然而,在 BluStar.NRW 供者队列中取消了 13 项工作,取消率几乎高出两倍(45%比 25%)。这项具有大型样本队列的单一登记分析清楚地表明,具有移民背景的造血干细胞供者是为具有相似种族背景的患者提供服务的充分供者群体。