背景:液滴数字PCR(ddPCR)广泛应用于监测可测量的残留病(MRD)。然而,关于异基因造血干细胞移植(allo-HSCT)后ddPCR-MRD监测的可行性研究有限,特别是同时靶向多个分子标记。
方法:我们的研究收集了2018年1月至2021年8月allo-HSCT后完全缓解的急性髓细胞性白血病(AML)或高危骨髓增生异常综合征(MDS)患者的样本,以评估移植后ddPCR-MRD监测是否可以识别复发风险高的患者。
结果:在152名患者中,移植后4个月内ddPCR检测MRD阳性58例(38.2%),变异等位基因频率中位数为0.198%。可检测的DTA突变(DNMT3A,TET2和ASXL1突变)在allo-HSCT后与复发风险增加无关。排除DTA突变后,ddPCR-MRD阳性患者的累积复发率明显较高(CIR,38.7%vs.9.7%,P<0.001)和较低的无复发生存率(RFS,55.5%与83.7%,P<0.001)和总生存期(OS,60.5%与90.5%,P<0.001)。在多变量分析中,非DTA基因的ddPCR-MRD阳性是CIR的独立不良预测因子(风险比[HR],4.02;P<0.001),RFS(HR,2.92;P=0.002)和OS(HR,3.12;P=0.007)。此外,ddPCR与多参数流式细胞术(MFC)的结合可以进一步准确地识别具有高复发风险的患者(F/M,HR,22.44;P<0.001,F+/M-,HR,12.46;P<0.001和F-/M+,HR,4.51;P=0.003)。
结论:ddPCR-MRD是预测具有非DTA基因的AML/MDS患者allo-HSCT后复发的可行方法,并且与MFC联合使用时更准确。
背景:ClinicalTrials.gov标识符:NCT06000306。2023年8月17日注册-回顾性注册(https://clinicaltrials.gov/study/NCT06000306?term=NCT06000306&rank=1)。
BACKGROUND: Droplet digital PCR (ddPCR) is widely applied to monitor measurable residual disease (MRD). However, there are limited studies on the feasibility of ddPCR-MRD monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially targeting multiple molecular markers simultaneously.
METHODS: Our study collected samples from patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) in complete remission after allo-HSCT between January 2018 and August 2021 to evaluate whether posttransplant ddPCR-MRD monitoring can identify patients at high risk of relapse.
RESULTS: Of 152 patients, 58 (38.2%) were MRD positive by ddPCR within 4 months posttransplant, with a median variant allele frequency of 0.198%. The detectable DTA mutations (DNMT3A, TET2, and ASXL1 mutations) after allo-HSCT were not associated with an increased risk of relapse. After excluding DTA mutations, patients with ddPCR-MRD positivity had a significantly higher cumulative incidence of relapse (CIR, 38.7% vs. 9.7%, P < 0.001) and lower rates of relapse-free survival (RFS, 55.5% vs. 83.7%, P < 0.001) and overall survival (OS, 60.5% vs. 90.5%, P < 0.001). In multivariate analysis, ddPCR-MRD positivity of non-DTA genes was an independent adverse predictor for CIR (hazard ratio [HR], 4.02; P < 0.001), RFS (HR, 2.92; P = 0.002) and OS (HR, 3.12; P = 0.007). Moreover, the combination of ddPCR with multiparameter flow cytometry (MFC) can further accurately identify patients at high risk of relapse (F+/M+, HR, 22.44; P < 0.001, F+/M-, HR, 12.46; P < 0.001 and F-/M+, HR, 4.51; P = 0.003).
CONCLUSIONS: ddPCR-MRD is a feasible approach to predict relapse after allo-HSCT in AML/MDS patients with non-DTA genes and is more accurate when combined with MFC.
BACKGROUND: ClinicalTrials.gov identifier: NCT06000306. Registered 17 August 2023 -Retrospectively registered ( https://clinicaltrials.gov/study/NCT06000306?term=NCT06000306&rank=1 ).