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基于流式细胞术的微小残留病(MRD)分析可识别出可能从异基因造血干细胞移植中获益的 AML 患者。

Flow cytometry-based measurable residual disease (MRD) analysis identifies AML patients who may benefit from allogeneic hematopoietic stem cell transplantation.

机构信息

Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.

King Saud Medical City, Riyadh, Saudi Arabia.

出版信息

Ann Hematol. 2024 Apr;103(4):1187-1196. doi: 10.1007/s00277-024-05639-6. Epub 2024 Jan 30.

DOI:10.1007/s00277-024-05639-6
PMID:38291275
Abstract

Measurable residual disease (MRD) monitoring independently predicts long-term outcomes in patients with acute myeloid leukemia (AML). Of the various modalities available, multiparameter flow cytometry-based MRD analysis is widely used and relevant for patients without molecular targets. In the transplant (HCT) setting, the presence of MRD pre-HCT is associated with adverse outcomes. MRD-negative remission status pre-HCT was also associated with longer overall (OS) and progression-free survival and a lower risk of relapse. We hypothesize that the combination of disease risk and MRD at the time of first complete remission (CR1) could identify patients according to the benefit gained from HCT, especially for intermediate-risk patients. We performed a retrospective analysis comparing the outcomes of HCT versus non-HCT therapies based on MRD status in AML patients who achieved CR1. Time-dependent analysis was applied considering time-to-HCT as a time-dependent covariate and compared HCT versus non-HCT outcomes according to MRD status at CR1. Among 336 patients assessed at CR1, 35.1% were MRD positive (MRD) post-induction. MRD patients benefitted from HCT with improved OS and relapse-free survival (RFS), while no benefit was observed in MRD patients. In adverse-risk patients, HCT improved OS (HR for OS 0.55; p = 0.05). In intermediate-risk patients, HCT benefit was not significant for OS and RFS. Intermediate-risk MRD patients were found to have benefit from HCT with improved OS (HR 0.45, p = 0.04), RFS (HR 0.46, p = 0.02), and CIR (HR 0.41, p = 0.02). Our data underscore the benefit of HCT in adverse risk and MRD intermediate-risk AML patients.

摘要

残留疾病(MRD)监测可独立预测急性髓系白血病(AML)患者的长期预后。在各种可用的方法中,基于多参数流式细胞术的 MRD 分析被广泛应用,且与无分子靶点的患者相关。在移植(HCT)环境中,HCT 前 MRD 的存在与不良预后相关。HCT 前 MRD 阴性缓解状态也与更长的总生存期(OS)和无进展生存期相关,并且复发风险较低。我们假设在首次完全缓解(CR1)时结合疾病风险和 MRD 可以根据 HCT 带来的获益来识别患者,尤其是对于中危患者。我们对在 CR1 时达到缓解的 AML 患者根据 MRD 状态进行 HCT 与非 HCT 治疗的结局进行了回顾性分析。考虑到 HCT 时间作为时间依赖性协变量,采用时间依赖性分析,根据 CR1 时的 MRD 状态比较 HCT 与非 HCT 的结局。在 336 名评估为 CR1 的患者中,35.1%的患者在诱导后呈 MRD 阳性(MRD)。MRD 患者从 HCT 中获益,OS 和无复发生存率(RFS)得到改善,而 MRD 患者则没有获益。在高危患者中,HCT 改善了 OS(OS 的 HR 为 0.55;p=0.05)。在中危患者中,HCT 对 OS 和 RFS 没有显著获益。对于中危 MRD 患者,我们发现 HCT 可改善 OS(HR 为 0.45,p=0.04)、RFS(HR 为 0.46,p=0.02)和 CIR(HR 为 0.41,p=0.02)。我们的数据强调了 HCT 在高危和中危 MRD 急性髓系白血病患者中的获益。

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本文引用的文献

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DNA Sequencing to Detect Residual Disease in Adults With Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant.DNA 测序检测造血细胞移植前急性髓系白血病成人患者的残留疾病。
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Pretransplant FLT3-ITD MRD assessed by high-sensitivity PCR-NGS determines posttransplant clinical outcome.通过高灵敏度聚合酶链反应-下一代测序评估的移植前FLT3-ITD微小残留病可确定移植后的临床结局。
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Allogeneic transplant can abrogate the risk of relapse in the patients of first remission acute myeloid leukemia with detectable measurable residual disease by next-generation sequencing.异基因移植可以通过下一代测序消除检测到的可测量残留疾病的首次缓解的急性髓系白血病患者的复发风险。
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