Jin Yan, Wang An-You, Wang Xing-Bing, Yang Hui-Zhi, Liu Xin
Department of Hematology, Anhui Provincial Hospital, Hefei 230001, Anhui Province, China.
Department of Hematology, Anhui Provincial Hospital, Hefei 230001, Anhui Province, China,E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Jun;30(3):737-743. doi: 10.19746/j.cnki.issn.1009-2137.2022.03.012.
To investigate the prognostic significance of dynamic detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) by 8-color flow cytometry.
MRD of 282 AML patients who achieved remission after initial therapy was detected by 8-color flow cytometry. MRD threshold for predicting recurrence was determined by receiver operating characteristic (ROC) curve, and time from MRD-positive to clinical recurrence was analyzed. The differences in overall survival (OS) time and relapse-free survival (RFS) time of patients with different MRD-changes were compared, and the related factors of recurrence in patients with MRD-negative were analyzed by univariate and logistic regression analysis.
ROC curve determined that the MFC-MRD threshold for predicting the recurrence of AML was 0.105%, and the recurrence rate of MRD-positive patients was significantly higher than that of MRD-negative patients [52.45% (75/143 cases) vs 35.97% (50/139 cases), P=0.005]. The patients in MRD persistent positive group and negative to positive group recurred earlier than those in positive to negative group and negative-positive fluctuation group (P<0.005). Survival analysis showed that OS and RFS time of patients with MRD persistent positive were significantly shorter than those of patients with MRD persistent negative, positive to negative, and negative-positive fluctuation (P<0.005). There was no significant difference in OS and RFS between MRD negative to positive group and MRD persistent positive group (P>0.005), either between MRD persistent negative group and MRD positive to negative group (P>0.005). Among 139 MRD-negative patients, 50 recurred. Univariate and logistic regression analysis showed that the risk of recurrence increased with the increase of white blood cells level (95%CI: 1.000-1.013, P=0.045). The risk of recurrence in patients without hematopoietic stem cell transplantation (HSCT) was 9.694 times higher than that in patients who received HSCT (95%CI: 1.720-54.651, P=0.010), and in the high-risk group was 5.848 times higher than that in the low-risk group (95%CI: 1.418-24.121, P=0.015).
The prognosis of AML patients with different MRD changes is significantly different. No matter MRD-positive or MRD-negative at the initial remission, dynamic detection of MRD after treatment is more helpful to accurately guide treatment.
探讨采用八色流式细胞术动态检测急性髓系白血病（AML）患者微小残留病（MRD）的预后意义。
采用八色流式细胞术检测282例初始治疗后获得缓解的AML患者的MRD。通过受试者工作特征（ROC）曲线确定预测复发的MRD阈值，并分析从MRD阳性到临床复发的时间。比较不同MRD变化患者的总生存（OS）时间和无复发生存（RFS）时间的差异，采用单因素和logistic回归分析对MRD阴性患者复发的相关因素进行分析。
ROC曲线确定预测AML复发的MFC-MRD阈值为0.105%，MRD阳性患者的复发率显著高于MRD阴性患者[52.45%（75/143例）对35.97%（50/139例），P=0.005]。MRD持续阳性组和阴性转阳性组患者的复发时间早于阳性转阴性组和阴性-阳性波动组（P<0.005）。生存分析显示，MRD持续阳性患者的OS和RFS时间显著短于MRD持续阴性、阳性转阴性和阴性-阳性波动患者（P<0.005）。MRD阴性转阳性组与MRD持续阳性组之间的OS和RFS无显著差异（P>0.005），MRD持续阴性组与MRD阳性转阴性组之间也无显著差异（P>0.005）。在139例MRD阴性患者中，50例复发。单因素和logistic回归分析显示，复发风险随白细胞水平升高而增加（95%CI：1.000-1.013，P=0.045）。未进行造血干细胞移植（HSCT）患者的复发风险是接受HSCT患者的9.694倍（95%CI：1.720-54.65l，P=0.010），高危组患者的复发风险是低危组的5.848倍（95%CI：1.418-24.121，P=0.015）。
不同MRD变化的AML患者预后差异显著。无论初始缓解时MRD阳性或阴性，治疗后动态检测MRD更有助于准确指导治疗。
