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[中危新诊断的年轻及中年急性髓系白血病患者巩固治疗前微小残留病的预后因素及预测价值]

[Prognostic Factors and Predictive Value of MRD before Consolidation Therapy in Middle-risk Newly Diagnosed Young and Middle-aged Patients with AML].

作者信息

Niu Zhi-Ying, Dang Hui-Bing, Yue Lei, Tian Qiu-Sheng

机构信息

Department of Blood Transfusion,The First Affiliated Hospital of Nanyang Medical College,Nanyang 473000, Henan Province, China.

Department of Hematology,The First Affiliated Hospital of Nanyang Medical College,Nanyang 473000, Henan Province, China,E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021 Apr;29(2):462-468. doi: 10.19746/j.cnki.issn.1009-2137.2021.02.025.

DOI:10.19746/j.cnki.issn.1009-2137.2021.02.025
PMID:33812416
Abstract

OBJECTIVE

To explore the prognostic factors of young and middle-aged patients with acute myeloid leukemia (AML) and the predictive value of minimal residual disease (MRD) before consolidation therapy.

METHODS

The clinical data of 262 middle-risk young and middle-aged patients with AML treated in our hospital from January 2010 to December 2018 were selected retrospectively. All the patients were reached morphological leukemia-free state (MLFS) after induction chemotherapy, the overall and subgroup clinical data of the selected patients were analyzed. Cox regression model was used to evaluate the independent prognostic factors of middle-risk newly diagnosed young and middle-aged patients.

RESULTS

Among the patients less than 40 years old treated by consolidation therapy with PR-CT and allo-HSCT regimens, the 5-year cumulative leukemia-free survival(LFS) rates were 40.92% and 63.51%(P=0.01)respectively, while those over 40 years old were 23.61% and 49.14%(P=0.00), respectively. The 5-year cumulative LFS rates of the patients treated by chemotherapy and achieved early remission and late remission were 63.51% and 41.33% (P=0.01), respectively. The 5-year cumulative overall survival(OS) rates of the patients treated by PR-CT and allo-HSCT regimens were 23.65% and 69.32% (P=0.00), respectively, and the 5-year cumulative LFS rates were 26.44% and 52.30% (P=0.01). Among the patients treated by PR-CT consolidation treatment, the MRD-negative and MRD-positive cases were 74 and 60 cases, respectively. The 5-year cumulative incidence of relapse rate in the MRD-negative subgroup was significantly lower than those in the MRD-positive subgroup (P<0.05), the 5-year LFS rate and OS rate of the patients in MRD-negative subgroup were significantly higher than those in MRD-positive subgroup (P<0.05). For the patients treated by allo-HSCT consolidation treatment, the MRD-negative and MRD-positive cases were 66 and 62 cases, respectively. The 5-year cumulative incidence of relapse rate of the patients in MRD-negative subgroup was significantly lower than those in MRD-positive subgroup(P<0.05), and the 5-year LFS and OS rates of the patients in MRD-negative subgroup were significantly higher than those in MRD-positive subgroup (P<0.05). The univariate analysis results showed that age, chromosome karyotype, MRD status after reaching MLFS, and consolidation treatment regime were all related to the prognosis of patients (P<0.05). The multivariate analysis results showed that age, MRD status after reaching MLFS, and consolidation therapy were the independent factors affecting the cumulative OS rate of the patients (P<0.05). Chromosome karyotype was an independent factor affecting the cumulative LFS rate of the patients (P<0.05). MRD status and consolidation treatment plan after reaching MLFS were the independent factors affecting the cumulative recurrence rate of the patients (P<0.05).

CONCLUSION

The OS rate of middle-risk young and middle-aged patients with newly diagnosed AML is independently related to age, MRD status after MLFS and consolidation therapy, while chromosome karyotype is independently related to cumulative LFS, and allo-HSCT consolidation therapy is recommended for middle-risk young and middle-aged AML patients after induction chemotherapy for MLFS, especially for those less than 40 years old and MRD positive before consolidation therapy.

摘要

目的

探讨中青年急性髓系白血病(AML)患者的预后因素及巩固治疗前微小残留病(MRD)的预测价值。

方法

回顾性选取2010年1月至2018年12月在我院治疗的262例中危中青年AML患者的临床资料。所有患者诱导化疗后均达到形态学无白血病状态(MLFS),对入选患者的总体及亚组临床资料进行分析。采用Cox回归模型评估新诊断中危中青年患者的独立预后因素。

结果

在接受PR-CT和异基因造血干细胞移植(allo-HSCT)方案巩固治疗的40岁以下患者中,5年累积无白血病生存率(LFS)分别为40.92%和63.51%(P = 0.01),而40岁以上患者分别为23.61%和49.14%(P = 0.00)。化疗后早期缓解和晚期缓解患者的5年累积LFS率分别为63.51%和41.33%(P = 0.01)。接受PR-CT和allo-HSCT方案治疗患者的5年累积总生存率(OS)分别为23.65%和69.32%(P = 0.00),5年累积LFS率分别为26.44%和52.30%(P = 0.01)。在接受PR-CT巩固治疗的患者中,MRD阴性和阳性病例分别为74例和60例。MRD阴性亚组的5年累积复发率显著低于MRD阳性亚组(P < 0.05),MRD阴性亚组患者的5年LFS率和OS率显著高于MRD阳性亚组(P < 0.05)。对于接受allo-HSCT巩固治疗的患者,MRD阴性和阳性病例分别为66例和62例。MRD阴性亚组患者的5年累积复发率显著低于MRD阳性亚组(P < 0.05),MRD阴性亚组患者的5年LFS率和OS率显著高于MRD阳性亚组(P < 0.05)。单因素分析结果显示,年龄、染色体核型、达到MLFS后的MRD状态及巩固治疗方案均与患者预后相关(P < 0.05)。多因素分析结果显示,年龄、达到MLFS后的MRD状态及巩固治疗是影响患者累积OS率的独立因素(P < 0.05)。染色体核型是影响患者累积LFS率的独立因素(P < 0.05)。达到MLFS后的MRD状态及巩固治疗方案是影响患者累积复发率的独立因素(P < 0.05)。

结论

新诊断中危中青年AML患者的OS率与年龄、MLFS后的MRD状态及巩固治疗独立相关,而染色体核型与累积LFS独立相关,对于诱导化疗达到MLFS后的中危中青年AML患者,推荐allo-HSCT巩固治疗,尤其是40岁以下且巩固治疗前MRD阳性的患者。

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