异基因造血干细胞移植（allo-HSCT）仍然是血液系统恶性肿瘤（HM）的关键治疗选择，尽管它存在很大的风险。高达 30% 的患者在 allo-HSCT 后复发，其中 2-5% 是供体来源的恶性肿瘤 (DDM)。 DDM 可能由供体的种系遗传易感性等位基因或克隆造血 (CH) 引起。基因检测越来越多地表明，患者和捐赠者的遗传因素会导致 DDM 和其他同种异体造血干细胞移植并发症的发生。 CEBPA、DDX41、GATA2 和 RUNX1 中的有害种系变异容易导致同种异体造血干细胞移植结果较差。 DDM 与 DNMT3A、ASXL1、JAK2 和 IDH2 中供体获得性体细胞 CH 变异相关，通常还伴有其他新变异。我们还没有证据来标准化异基因造血干细胞移植之前的供体基因测序。骨髓恶性肿瘤患者及其相关供体应考虑是否存在遗传性 HM 疾病，并且对无关供体的筛查应包括血细胞减少症和 HM 的家族史和个人史。优秀的多学科护理对于确保肿瘤内科医生、遗传咨询师、受赠者和潜在捐赠者之间有效的筛查和必要的讨论至关重要。同种异体造血干细胞移植后，通过基因检测监测 HM 复发，可以有效地对捐献者进行基因测序，因为移植的造血系统来自捐献者，这对向患者和捐献者披露信息提出了伦理挑战。我们鼓励考虑最近的国家骨髓捐赠计划政策，该政策允许捐赠者选择在异基因造血干细胞移植后检测其遗传变异的通知，并在可行时提供适当的遗传咨询。我们期待对种系和获得性体细胞遗传变异对造血干细胞动员/植入、移植物抗宿主病和 DDM 的影响进行前瞻性研究，以通过了解遗传风险来促进改善结果。版权所有 © 2023。由 Elsevier Inc. 出版。

Allogeneic hematopoietic stem cell transplant (allo-HSCT) remains a key treatment option for hematologic malignancies (HMs), although it carries significant risks. Up to 30% of patients relapse after allo-HSCT, of which 2-5% are donor-derived malignancies (DDM). DDM can arise from a germline genetic predisposition allele or clonal hematopoiesis (CH) in the donor. Increasingly, genetic testing reveals that patient and donor genetic factors contribute to the development of DDM and other allo-HSCT complications. Deleterious germline variants in CEBPA, DDX41, GATA2, and RUNX1 predispose to inferior allo-HSCT outcomes. DDM has been linked to donor acquired somatic CH variants in DNMT3A, ASXL1, JAK2, and IDH2, often with additional new variants. We do not yet have evidence to standardize donor genetic sequencing prior to allo-HSCT. The presence of hereditary HM disorders should be considered in patients with myeloid malignancies and their related donors, and screening of unrelated donors should include family and personal history of cytopenias and HMs. Excellent multidisciplinary care is critical to ensure efficient timelines of screening and necessary discussions among medical oncologists, genetic counselors, recipients, and potential donors. After allo-HSCT, HM relapse monitoring with genetic testing effectively results in genetic sequencing of the donor as the transplanted hematopoietic system is donor derived, which presents ethical challenges for disclosure to patients and donors. We encourage consideration of the recent National Marrow Donor Program policy that allows donors to opt in for notification about detection of their genetic variants after allo-HSCT, with appropriate genetic counseling when feasible. We look forward to prospective investigation of the impact of germline and acquired somatic genetic variants on hematopoietic stem cell mobilization/engraftment, graft versus host disease, and DDM to facilitate improved outcomes through knowledge of genetic risk.Copyright © 2023. Published by Elsevier Inc.