中危初诊中青年AML患者预后的影响因素及巩固治疗前MRD预测价值研究

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

目的:探讨中危初诊中青年急性髓系白血病(AML)患者预后的影响因素及巩固治疗前微小残留病变(MRD)预测价值。方法:回顾性选取本院2010年1月-2018年12月收治中危初诊中青年AML共262例,所有患者均在诱导化疗后达形态学无白血病状态(MLFS),对患者的总体和亚组临床数据进行分析。采用Cox回归模型评价中危初诊中青年AML患者的预后独立影响因素。结果:<40岁的患者中,巩固治疗接受PR-CT和allo-HSCT方案5年累积无白血病生存(LFS)率分别为40.92%、63.51%(P=0.01);而≥40岁的患者则分别为23.61%、49.14%(P=0.00);诱导化疗早期缓解和晚期缓解5年累积LFS率分别为63.51%、41.33%(P=0.01);接受PR-CT和allo-HSCT方案治疗5年累积总生存(OS)率分别为23.65%、69.32%(P=0.00),5年累积LFS率分别为26.44%、52.30%(P=0.01)。接受PR-CT巩固治疗的患者中,MRD阴性和阳性分别为74和60例;MRD阴性亚组5年累积复发率显著低于MRD阳性亚组(P<0.05);接受PR-CT患者中,MRD阴性亚组5年LFS率和OS率均显著高于MRD阳性亚组(P<0.05)。接受allo-HSCT巩固治疗的患者中,MRD阴性和阳性分别为66和62例;MRD阴性亚组5年累积复发率显著低于MRD阳性亚组(P<0.05);allo-HSCT患者中,MRD阴性亚组5年LFS率和OS率均显著高于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MLFS后MRD状态及巩固治疗方案均与患者预后有关(P<0.05)。多因素分析结果显示,年龄、达MLFS后MRD状态及巩固治疗方案是患者累积OS率的独立影响因素(P<0.05);染色体核型是患者累积LFS率的独立影响因素(P<0.05);达MLFS后MRD状态和巩固治疗方案是影响患者累积复发率的独立影响因素(P<0.05)。结论:中危初诊中青年AML患者总生存与年龄、达MLFS后MRD状态及巩固治疗方案独立相关,而染色体核型则与患者累积LFS独立相关;对于中危中青年AML患者诱导化疗达MLFS后推荐接受allo-HSCT进行巩固治疗,尤其适用于<40岁且巩固治疗前MRD阳性人群。

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(M RD)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%(TP=0.01),respectively.The 5-vear 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 MRDnegative and MRD-ositive 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 MRDpositive 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).M RD 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.