可测量的残留疾病（MRD）评估为异基因造血细胞移植（alloHCT）结果提供了一种有吸引力的预测指标。细胞外DNA（cfDNA）已被应用于各种肿瘤的诊断、早期检测和疾病负担监测，但它作为髓系恶性肿瘤的MRD检测方法尚未进行系统评估。我们的目的是确定骨髓（BM）和cfDNA MRD之间的不同敏感性，并评估cfDNA MRD对alloHCT结果的影响。我们使用了技术和临床验证队列，包括82名参与临床试验（骨髓移植临床试验网络-0201和0402）的患者。外显错误修正的靶向测序在血浆和BM来源的DNA上进行。我们证明94.6%（范围为93.9-95.3）的cfDNA来自造血组织。突变等位基因的比例在BM和cfDNA中是一致的（rho = 0.8; P < .0001），然而，cfDNA似乎更敏感地检测到变异等位基因频率（VAF）<0.26%的克隆。与持续MRD的患者相比，alloHCT后90天（D90）cfDNA-MRD清除与改善的无复发生存（RFS，中位生存时间未达到vs 5.5个月; P < .0001）和总生存（OS，中位生存时间未达到vs 7.3个月; P < .0001）相关。无论alloHCT前的MRD如何，D90 cfDNA MRD与较差的2年OS（16.7% vs 84.8%; P < .0001）和RFS（16.7% vs 80.7%; P < .0001）相关。cfDNA似乎是一种准确、微创的BM采集替代方法，可用于MRD评估，并在接受alloHCT的骨髓恶性肿瘤患者中具有重要的预后影响。© 2023年 by The American Society of Hematology. 根据创作共用许可-非商业性-无衍生物4.0国际的条款（CC BY-NC-ND 4.0），仅允许进行非商业性、无衍生物的使用，需署名。保留所有其他权利。

The measurable residual disease (MRD) assessment provides an attractive predictor of allogeneic hematopoietic cell transplnat (alloHCT) outcomes. Cell-free DNA (cfDNA) has been applied to diagnosis, early detection, and disease burden monitoring in various tumors, but its utility as an MRD test in myeloid malignancies has not been systematically evaluated. We sought to determine the differential sensitivity between bone marrow (BM) and cfDNA MRD and to assess the effect of cfDNA MRD on alloHCT outcomes. The technical and clinical validation cohorts, including 82 patients participating in clinical trials (Bone Marrow Transplant Clinical Trials Network-0201 and 0402), were used. Ultradeep error-corrected targeted sequencing was performed on plasma and BM-derived DNA. We demonstrated that 94.6% (range, 93.9-95.3) of cfDNA was derived from hematopoietic tissue. The mutant allele fraction was congruent between BM and cfDNA (rho = 0.8; P < .0001); however, cfDNA seemed to be more sensitive in detecting clones with a variant allele frequency (VAF) of <0.26%. cfDNA-MRD clearance by day 90 after alloHCT (D90) was associated with improved relapse-free survival (RFS, median survival not reached vs 5.5 months; P < .0001) and overall survival (OS, median survival not reached vs 7.3 months; P < .0001) when compared with patients with persistent MRD. Irrespective of pre-alloHCT MRD, D90 cfDNA MRD was associated with inferior 2-year OS (16.7% vs 84.8%; P < .0001) and RFS (16.7% vs 80.7%; P < .0001). cfDNA seems to be an accurate, minimally invasive alternative to BM aspirates in MRD assessment and confers important prognostic implications in patients with myeloid malignancies undergoing alloHCT.© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.