Donor-Derived Malignancy and Transplantation Morbidity: Risks of Patient and Donor Genetics in Allogeneic Hematopoietic Stem Cell Transplantation

作者：Lacey Williams, Kirsten M. Williams, Nancy Gillis, Kelly L. Bolton, Frédérik Damm, Natalie Deuitch, Nosha Farhadfar, Usama Gergis, Sioḃán Keel, Fotios V. Michelis, Sandhya R. Panch, Christopher C. Porter, Lara E. Sucheston‐Campbell, Roni Tamari, Heather E. Stefanski, Lucy A. Godley, Catherine Lai · 发表于：Transplantation and Cellular Therapy · 年份：2023 · DOI：10.1016/j.jtct.2023.10.018 · 被引用次数：34 · 研究领域：Acute Myeloid Leukemia Research、Hematopoietic Stem Cell Transplantation、Acute Lymphoblastic Leukemia research

Allogeneic hematopoietic stem cell transplantation (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 up to 2% to 5% are donor-derived malignancies (DDMs). DDMs 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 cytopenia and HMs. Excellent multidisciplinary care is critical to ensure efficient timelines for 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 t...