Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Sci Transl Med. 2012 Jul 25;4(144):144ra101. doi: 10.1126/scitranslmed.3003974.
Blood malignancies can be cured with hematopoietic cell transplantation from human leukocyte antigen (HLA)-matched unrelated donors; however, acute graft-versus-host disease (GVHD) affects up to 80% of patients and contributes to increased mortality. To test the hypothesis that undetected patient-donor differences for non-HLA genetic variation within the major histocompatibility complex (MHC) could confer risks after HLA-matched transplantation, we conducted a discovery-validation study of 4205 transplants for 1120 MHC region single-nucleotide polymorphisms (SNPs). Two SNPs were identified as markers for disease-free survival and acute GVHD. Among patients with two or more HLA-matched unrelated donors identified on their search, SNP genotyping of patients and their potential donors demonstrated that most patients have a choice of SNP-matched donors. In conclusion, the success of HLA-matched unrelated donor hematopoietic cell transplantation depends on non-HLA MHC region genetic variation. Prospective SNP screening and matching provides an approach for lowering risks to patients.
血液恶性肿瘤可以通过来自人类白细胞抗原（HLA）匹配的无关供体的造血细胞移植治愈；然而，急性移植物抗宿主病（GVHD）影响多达 80%的患者，并导致死亡率增加。为了验证这样一个假设，即在 HLA 匹配移植后，主要组织相容性复合体（MHC）内非 HLA 遗传变异的未检测到的患者-供体差异可能带来风险，我们对 1120 个 MHC 区域单核苷酸多态性（SNP）的 4205 例移植进行了发现-验证研究。鉴定出两个 SNP 作为无病生存和急性 GVHD 的标志物。在他们的搜索中确定了两个或更多 HLA 匹配的无关供体的患者中，对患者及其潜在供体的 SNP 基因分型表明，大多数患者都有选择 SNP 匹配供体的机会。总之，HLA 匹配的无关供体造血细胞移植的成功取决于非 HLA MHC 区域的遗传变异。前瞻性 SNP 筛查和匹配为降低患者风险提供了一种方法。
