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用于预测接受同种异体移植的急性髓系白血病患者复发的白血病干细胞:一项前瞻性研究的长期随访

Leukemia stem cells for relapse prediction in AML patients receiving allografts: long-term follow-up of a prospective study.

作者信息

Li Si-Qi, Xu Lan-Ping, Wang Yu, Zhang Xiao-Hui, Chen Huan, Chen Yu-Hong, Wang Feng-Rong, Han Wei, Sun Yu-Qian, Yan Chen-Hua, Lv Meng, Tang Fei-Fei, Mo Xiao-Dong, Liu Kai-Yan, Huang Xiao-Jun, Chang Ying-Jun

机构信息

Peking University People's Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Beijing, China.

Peking-Tsinghua Center for Life Sciences, Beijing, China.

出版信息

Bone Marrow Transplant. 2025 Aug 23. doi: 10.1038/s41409-025-02699-8.

Abstract

In this study, we explored the ability of leukemia stem cell (LSC)-based method and traditional multiparameter flow cytometry (MFC) assay to predict leukemia relapse after long-term follow-up. 360 AML patients who received allografts between July 2018 and November 2019 were prospectively enrolled. Patients with positive measurable residual disease (MRD) based on CD34CD38cocktail LSCs (≥0.004%) exhibited a greater 5-year cumulative incidence of relapse (CIR) (49.7% vs. 8.5%, P < 0.001), inferior leukemia-free survival (LFS) (48.2% vs. 84.4%, P < 0.001) and inferior overall survival (OS) (59.7% vs. 82.8%, P < 0.001), than did patients without CD34CD38cocktail LSCs (<0.004%). Patients with detectable traditional MFC-MRD exhibited a greater CIR than patients without MRD (45.8% vs. 10.9%, P < 0.001), thereby leading to decreased LFS (54.2% vs. 81.9%, P < 0.001) and decreased OS (56.0% vs. 85.9%, P = 0.001). Compared with traditional MFC-MRD, LSCs-based MRD assay demonstrated high sensitivity (52.4% vs. 33.3%), high C-index (0.72 vs. 0.65) and high Youden index (0.44 vs. 0.27). The median time from LSCs positivity to relapse was longer than the median time from traditional MRD positivity to relapse (144 days vs. 65 days, P = 0.012). Our data confirmed the superiority of the LSC-based MRD assay compared to traditional MFC MRD methods in AML patients who received allografts after long-term follow-up.

摘要

在本研究中,我们探讨了基于白血病干细胞(LSC)的方法和传统多参数流式细胞术(MFC)检测在长期随访后预测白血病复发的能力。前瞻性纳入了2018年7月至2019年11月间接受同种异体移植的360例急性髓系白血病(AML)患者。基于CD34CD38鸡尾酒式LSC(≥0.004%)检测到可测量残留病(MRD)阳性的患者,其5年累积复发率(CIR)更高(49.7%对8.5%,P<0.001),无白血病生存期(LFS)更差(48.2%对84.4%,P<0.001),总生存期(OS)更差(59.7%对82.8%,P<0.001),而未检测到CD34CD38鸡尾酒式LSC(<0.004%)的患者则不然。检测到传统MFC-MRD的患者比未检测到MRD的患者有更高的CIR(45.8%对10.9%,P<0.001),从而导致LFS降低(54.2%对81.9%,P<0.001)和OS降低(56.0%对85.9%,P = 0.001)。与传统MFC-MRD相比,基于LSC的MRD检测显示出高敏感性(52.4%对33.3%)、高C指数(0.

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