Clinical Research Division, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, USA.
Department of Medicine, University of Washington (UW), Seattle, WA, USA.
Bone Marrow Transplant. 2021 May;56(5):1090-1098. doi: 10.1038/s41409-020-01149-x. Epub 2020 Dec 1.
Cord blood transplantation (CBT) is associated with low risk of leukemia relapse. Mechanisms underlying antileukemia benefit of CBT are not well understood, however a previous study strongly but indirectly implicated cells from the mother of the cord blood (CB) donor. A fetus acquires a small number of maternal cells referred to as maternal microchimerism (MMc) and MMc is sometimes detectable in CB. From a series of 95 patients who underwent double or single CBT at our center, we obtained or generated HLA-genotyping of CB mothers in 68. We employed a technique of highly sensitive HLA-specific quantitative-PCR assays targeting polymorphisms unique to the CB mother to assay CB-MMc in patients post-CBT. After additional exclusion criteria, CB-MMc was evaluated at multiple timepoints in 36 patients (529 specimens). CB-MMc was present in seven (19.4%) patients in bone marrow, peripheral blood, innate and adaptive immune cell subsets, and was detected up to 1-year post-CBT. Statistical trends to lower relapse, mortality, and treatment failure were observed for patients with vs. without CB-MMc post-CBT. Our study provides proof-of-concept that maternal cells of the CB graft can be tracked in recipients post-CBT, and underscore the importance of further investigating CB-MMc in sustained remission from leukemia following CBT.
脐带血移植(CBT)与白血病复发风险低相关。然而,CBT 抗白血病益处的机制尚不清楚,先前的一项研究强烈但间接地暗示了脐带血(CB)供体母亲的细胞。胎儿会获得少量被称为母体微嵌合体(MMc)的母体细胞,并且有时可以在 CB 中检测到 MMc。在我们中心接受双份或单份 CBT 的 95 例患者系列中,我们获得或生成了 68 例 CB 母亲的 HLA 基因分型。我们采用针对 CB 母亲特有的高度敏感 HLA 特异性定量 PCR 检测技术,在 CBT 后检测患者的 CB-MMc。在进一步排除标准后,在 36 例患者(529 个标本)中多个时间点评估了 CB-MMc。7 例(19.4%)患者的骨髓、外周血、固有和适应性免疫细胞亚群中存在 CB-MMc,并在 CBT 后长达 1 年检测到。与无 CB-MMc 患者相比,有 CB-MMc 患者的复发、死亡率和治疗失败的统计趋势较低。我们的研究提供了证据表明,CB 移植物中的母体细胞可以在 CBT 后在受体内被追踪,并强调了进一步研究 CBT 后白血病持续缓解中 CB-MMc 的重要性。