German Immunogenetics Society (DGI), Munich; Institute for Experimental Cellular Therapy, University Hospital Essen; German Consortium for Translational Cancer Research, Essen-Düsseldorf Site; German Registry for Hematopoietic Cell Transplantation (DRST), Essen; Institute for Immunology, University Hospital Heidelberg.
Dtsch Arztebl Int. 2023 Apr 14;120(15):261-268. doi: 10.3238/arztebl.m2023.0031.
In Germany, each year over 3000 patients with malignant and non-malignant hematologic and systemic diseases are treated by allo - geneic hematopoietic cell transplantation (HCT). Genetic donor-recipient disparities, especially those concerning variable human leukocyte antigens (HLA), mediate both an immunotherapeutic effect and the risk of damage to healthy tissues ("graft-versus-host disease"). The adoption of evidencebased strategies for donor selection has been crucial for the continuous improvement of survival rates after allogeneic HCT, with over 50% of patients transplanted for standard indications-such as early-stage acute myeloid leukemia-alive at three years post-transplant.
The PubMed database was selectively searched for literature on immunogenetic and clinical factors relevant to allogeneic HCT, as part of the process of establishing a German consensus statement on HCT donor selection.
The most important factor in donor selection is a match for the five major HLA loci (HLA-A, -B, -C, -DR, -DQ), either in genetically HLAidentical siblings or in unrelated but fully HLA-compatible donors from international registries. Additional selection criteria for the latter include com - patibility for the HLA-DP locus, donor age and sex, cytomegalovirus serostatus, and blood group. Related donors identical for only 50% of the HLA genes (haploidentical donors) as well as unrelated donors with a single HLA mismatch are both valid alternatives although they are associated with an up to 10% higher risk of mortality.
The refinement of donor selection strategies has been instrumental for the continuous improvement of patient survival rates after allogeneic HCT witnessed over the past decades. An interdisciplinary approach to donor selection based on up-to-date scientific evidence is crucial for optimizing patient outcomes.
在德国,每年有超过 3000 名患有恶性和非恶性血液系统和全身性疾病的患者接受同种异体造血细胞移植(HCT)治疗。遗传上的供体-受者差异,特别是那些与可变的人类白细胞抗原(HLA)有关的差异,既介导了免疫治疗效果,又增加了对健康组织的损伤风险(“移植物抗宿主病”)。采用基于证据的供者选择策略对于提高同种异体 HCT 后的生存率至关重要,超过 50%的患者在移植后三年时因标准适应症(如早期急性髓细胞白血病)而存活。
作为制定德国关于 HCT 供者选择的共识声明的一部分,我们选择性地在 PubMed 数据库中搜索了与同种异体 HCT 相关的免疫遗传学和临床因素的文献。
供者选择最重要的因素是在遗传上 HLA 完全相同的兄弟姐妹或来自国际登记处的完全 HLA 匹配的无关供者中,五个主要 HLA 位点(HLA-A、-B、-C、-DR、-DQ)匹配。后者的其他选择标准包括 HLA-DP 位点的相容性、供者年龄和性别、巨细胞病毒血清状态和血型。仅 HLA 基因 50%相同的相关供者(半相合供者)以及具有单个 HLA 错配的无关供者也是有效的替代方案,尽管它们与高达 10%的死亡率增加相关。
过去几十年来,同种异体 HCT 后患者生存率的持续提高,离不开供者选择策略的不断完善。基于最新科学证据的供者选择的跨学科方法对于优化患者结局至关重要。