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[急性髓系白血病化疗不同时间点流式细胞术微小残留病检测对预后的影响]

[Effect of Flow Cytometric MRD Detection at Different Time Points during AML Chemotherapy on Prognosis].

作者信息

Ju Rui-Xue, Sun Feng-Qiang, Wang Yu-Hui

机构信息

Department of Clinical Laboratory Examination, Weifang People's Hospital, Weifang 261041, Shandong Province, China.

Department of Clinical Laboratory Examination, Weifang People's Hospital, Weifang 261041, Shandong Province, China.E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2024 Aug;32(4):1051-1057. doi: 10.19746/j.cnki.issn.1009-2137.2024.04.012.

Abstract

OBJECTIVE

To investigate the effect of flow cytometric minimal residual disease (MRD) detection at different time points during AML chemotherapy on prognosis.

METHODS

130 adult primary AML patients diagnosed and standardized with chemotherapy from March 2018 to March 2022 were retrospectively analyzed, MRD was detected by flow cytometry, Kaplan-Meier curves was used for survival analysis and log-rank test was used for variance analysis, and univariate and multifactor influencing patient survival with COX proportional risk regression model analysis. Cumulative incidence rate (CIR) analysis with competing risk model and variance analysis using Fine-Gray.

RESULTS

There were 81 CR1, 26 CR2, 14 PR, and 9 NR patients in 130 patients. OS of the CR1 group was higher than that in the CR2, PR,and NR groups. OS of the CR2 group was higher than that in the PR group, but there was no statistically difference compared to the NR group. There was no statistically difference in OS between the PR and NR groups. 107 patients in CR1 and CR2 were grouped according to MRD detected by flow cytometry, and after the first induction chemotherapy, for patients in the MRD and MRD groups, the 4-year expected RFS rates were 65.3% and 27.9% respectively, the 4-year expected OS rates were 58.7% and 41.4% respectively, and the 4-year expected CIR were 34.7% and 69.7% respectively, with statistically significant differences between 2 groups (χ=6.639, =0.010; χ=6.131, =0.013 and χ=6.637, =0.010). After the second chemotherapy, for patients in the MRD and MRD groups, the 4-year expected RFS rates were 50.8% and 37.9% respectively, the 4-year expected OS rates were 49.2% and 44.5% respectively, and the 4-year expected CIR were 49.2% and 59.5% respectively, with no statistically significant differences between 2 groups (χ=1.475, =0.225; χ=2.432, =0.119 and χ=1.416, =0.234). During consolidation therapy, for patients in the MRD and MRD groups, the 4-year expected RFS rates were 51.9% and 29.6% respectively, the 4-year expected OS rates were 67.5% and 24.6% respectively, and the 4-year expected CIR were 48.1% and 70.4% respectively, with statistically significant differences between 2 groups (χ=20.982, < 0.001; χ=17.794, < 0.001 and χ=19.879, < 0.001). For patients with MRD at all three time points and positive at either time point, the 4-year expected RFS rates were 69.9% and 33.3% respectively, the 4-year expected OS rates were 59.1% and 44.7% respectively, and the 4-year expected CIR were 30.1% and 65.1% respectively, with statistically significant differences between 2 groups (χ=7.367, =0.007; χ=6.042, =0.014 and χ=7.662, =0.006). Univariate analysis showed that karyotype at high risk of chromosome was an unfavorable factor affecting patients' RFS and OS, while 2 cycles of induction chemotherapy achieved CR, MRD after the first induction chemotherapy and MRD after the second induction chemotherapy was a protective factor affecting patients' RFS and OS. MRD during consolidation therapy and MRD at all three time points were all protective factors affecting patients' RFS, OS and CIR. Multivariate analysis showed that induction chemotherapy for 2 cycles achieved CR was a protective factor affecting patients' RFS and CIR, and MRD during consolidation therapy was a protective factor affecting patients' RFS, OS and CIR.

CONCLUSION

Early achievement of CR and MRD in adult AML patients, especially MRD during consolidation therapy, is a marker of good prognosis, and flow cytometry is the most commonly used method for MRD detection in AML patients.

摘要

目的

探讨急性髓系白血病(AML)化疗不同时间点流式细胞术检测微小残留病(MRD)对预后的影响。

方法

回顾性分析2018年3月至2022年3月确诊并接受标准化化疗的130例成年原发性AML患者,采用流式细胞术检测MRD,应用Kaplan-Meier曲线进行生存分析,采用log-rank检验进行方差分析,并运用COX比例风险回归模型分析影响患者生存的单因素和多因素。采用竞争风险模型进行累积发病率(CIR)分析,并使用Fine-Gray进行方差分析。

结果

130例患者中,完全缓解(CR1)81例,部分缓解(CR2)26例,PR 14例,未缓解(NR)9例。CR1组总生存期(OS)高于CR2、PR和NR组。CR2组OS高于PR组,但与NR组相比无统计学差异。PR组和NR组OS无统计学差异。将CR1和CR2的107例患者根据流式细胞术检测的MRD进行分组,首次诱导化疗后,MRD阴性和阳性组患者的4年预期无复发生存率(RFS)分别为65.3%和27.9%,4年预期OS率分别为58.7%和41.4%,4年预期CIR分别为34.7%和69.7%,两组间差异有统计学意义(χ=6.639,P =0.010;χ=6.131,P =0.013;χ=6.637,P =0.010)。第二次化疗后,MRD阴性和阳性组患者的4年预期RFS率分别为50.8%和37.9%,4年预期OS率分别为49.2%和44.5%,4年预期CIR分别为49.2%和59.5%,两组间无统计学差异(χ=1.475,P =0.225;χ=2.432,P =0.119;χ=1.416,P =0.234)。巩固治疗期间,MRD阴性和阳性组患者的4年预期RFS率分别为51.9%和29.6%,4年预期OS率分别为67.5%和24.6%,4年预期CIR分别为48.

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