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实时定量聚合酶链反应监测核心结合因子急性髓系白血病微小残留病对移植结果的意义。

Significance of minimal residual disease monitoring by real-time quantitative polymerase chain reaction in core binding factor acute myeloid leukemia for transplantation outcomes.

机构信息

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

出版信息

Cancer. 2020 May 15;126(10):2183-2192. doi: 10.1002/cncr.32769. Epub 2020 Feb 26.

Abstract

BACKGROUND

Despite the well-defined role of minimal residual disease (MRD) monitoring by real-time quantitative polymerase chain reaction (RT-PCR) for RUNX1/RUNX1T1 and CBFB-MYH11 transcripts in core binding factor (CBF) acute myeloid leukemia (AML) after intensive chemotherapy, there has been a paucity of data assessing the utility of MRD monitoring at and after allogeneic hematopoietic stem cell transplantation (HSCT).

METHODS

Patients with CBF AML who underwent HSCT in complete remission (first or second) from January 2007 through December 2018 were included in this analysis.

RESULTS

MRD by polymerase chain reaction at HSCT was assessed in 50 of 76 patients, and 44 (88%) had evidence of MRD (MRDpos). MRDpos patients had 3-year overall survival (OS) and leukemia-free survival (LFS) rates of 69.3% and 66.3%, respectively. Six MRD-negative patients had 3-year OS and LFS rates of 100% and 100%, respectively. Thirty-five of the 70 evaluable patients (50%) had a day +100 MRD assessment by RT-PCR, and 14 (40%) were MRDpos. The presence of MRD by RT-PCR on day +100 was not associated with lower estimates of LFS (75% vs 82.2%; P = .3) but was associated with a higher relapse incidence, although the difference did not reach statistical significance (27.6% vs 9.7%; P = .2).

CONCLUSIONS

Durable complete remissions can be achieved in patients with CBF AML with HSCT even if they are MRDpos by RT-PCR at HSCT. The clinical impact of frequent MRD monitoring for identifying a group at high risk for early relapse and then for determining the best time point for therapeutic interventions to prevent impending relapse warrants investigation in prospectively designed clinical trials.

摘要

背景

尽管实时定量聚合酶链反应(RT-PCR)检测 RUNX1/RUNX1T1 和 CBFB-MYH11 转录本的微小残留病(MRD)在强化化疗后的核心结合因子(CBF)急性髓系白血病(AML)中具有明确的作用,但评估异基因造血干细胞移植(HSCT)前后 MRD 监测效用的数据却很少。

方法

本研究纳入了 2007 年 1 月至 2018 年 12 月期间在完全缓解(首次或第二次)状态下接受 HSCT 的 CBF-AML 患者。

结果

50 例患者在 HSCT 时接受了聚合酶链反应检测 MRD,其中 44 例(88%)MRD 阳性(MRDpos)。MRDpos 患者的 3 年总生存率(OS)和无白血病生存率(LFS)分别为 69.3%和 66.3%。6 例 MRD 阴性患者的 3 年 OS 和 LFS 率分别为 100%和 100%。70 例可评估患者中有 35 例(50%)在第+100 天进行了 RT-PCR 评估,其中 14 例(40%)MRDpos。第+100 天 RT-PCR 检测到 MRD 与较低的 LFS 估计值无关(75%比 82.2%;P=0.3),但与较高的复发发生率相关,尽管差异无统计学意义(27.6%比 9.7%;P=0.2)。

结论

即使在 HSCT 时 RT-PCR 检测到 MRDpos,接受 HSCT 的 CBF-AML 患者也能获得持久的完全缓解。频繁进行 MRD 监测以识别早期复发风险较高的患者,并确定进行治疗干预以预防即将发生的复发的最佳时间点,从而改善患者预后,这一临床意义值得在前瞻性设计的临床试验中进一步研究。

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