134例老年急性髓系白血病的临床特点及预后分析

Clinical features and prognosis of 134 elderly patients with acute myeloid leukemia

目的:分析老年急性髓系白血病(acute myeloid leukemia,AML)(非早幼粒细胞白血病)的临床特点,治疗方式以及疗效和预后特点。方法:收集2015年1月至2023年2月北京大学国际医院收治的134例老年AML患者资料,回顾性分析患者初诊时的白细胞计数、骨髓原始细胞计数、细胞遗传学及分子学特点、ELN危险分层,根据不同治疗方案将患者分为高强度化疗组和低剂量治疗组,观察在治疗过程中强化疗是否能给患者带来生存获益以及影响老年患者生存的因素。结果:高强度化疗患者36例,22例完全缓解(complete response,CR)(61.1%),低剂量治疗90例中46例获得CR(51.1%),其中19例阿扎胞苷(AZA)联合维奈克拉(VEN)治疗换着中14例获得CR(73.7%);高强度化疗与低剂量治疗的总生存期(overall survival,OS)分别为15个月和14.5个月(P=0.226)。欧洲白血病网(ELN)危险分层低、中、高危组患者OS分别为18、14、9个月(P=0.009),低危组高强度化疗和低剂量治疗的OS分别为22个月和15个月(P=0.745),中危组分别为9个月和15个月(P=0.783),高危组分别为9个月和8个月(P=0.739)。强化疗(36例)与阿扎胞苷+维奈克拉治疗(19例)相比OS分别为15个月和17个月(P=0.689)。TP53基因突变者6例,预后明显差于无突变者,中位生存期分别为2个月和14个月(P=0.004)。低、中、高危患者的1年生存率为79%、53%和44%,3年生存率分别为41%、20%和3%。多因素分析显示外周血高白细胞计数(P=0.034)、ELN危险分层(P=0.002)、合并症(P=0.017)与OS相关,而治疗强度、年龄、性别、骨髓原始细胞计数与OS无明显相关性。高强度化疗在老年AML中没有显示明显的生存获益,但这一结果在低危患者中有待于进一步观察。TP53突变者预后较差。多因素分析预测老年AML的生存期时,基线的分子学特征、白细胞计数、合并症比治疗强度更重要。

Objective:To investigate the clinical features,therapeutic methods,therapeutic efficacy,and prognostic characteristics of older patients with acute myeloid leukemia(AML).Methods:We collected data from 134 older patients with AML treated at Peking University International Hospital between January 2015 and February 2023.White blood cell count,bone marrow primitive cell count,cytogenetic and molecular characteristics,and European LeukemiaNet(ELN)risk stratification at initial diagnosis were retrospectively analyzed.Patients were assigned into two groups according to treatment plan―high-intensity chemotherapy and low-dose treatment―to determine whether intensive chemotherapy would yield survival benefits during treatment and the factors affecting survival.Results:Among 36 patients treated with high-intensity chemotherapy,22(61.1%)achieved complete response(CR);among 90 treated with low-intensity therapy,46(51.1%)achieved CR;and among 19 treated with azacitidine(AZA)+venecra(VEN),14(73.7%)achieved CR.Median overall survival(OS)was 15 months for high-intensity chemotherapy and 14.5 months for low-intensity treatment(P=0.226).According to ELN risk stratification,patients in the low,medium,and high risk groups exhibited OS of 18,14,and 9 months,respectively(P=0.009).OS for high-intensity chemotherapy and low-dose therapy was 22 and 15 months in the low-risk group(P=0.745),9 and 15 months in the mediumrisk group(P=0.783),and 9 and 8 months in the high-risk group(P=0.739),respectively.Patients in the intensive chemotherapy group(n=36)had an OS of 15 and 17 months(P=0.689)compared with AZA+VEN treatment(n=19).The prognosis of six patients with TP53 mutation was significantly worse than those without the mutation,and the median OS was 2 months and 14 months,respectively(P=0.004).One-and 3-year survival rates for the low-,medium-and high-risk groups were 79%,53%,and 44%,and 41%,20%,and 3%,respectively.Multivariate analysis revealed that high peripheral blood white blood cell count(P=0.034),ELN risk stratification(P=0.002),and complications(P=0.017)were correlated with OS,while treatment intensity,age,sex,and bone marrow primitive cell count were not significantly correlated with OS.Conclusions:High-intensity chemotherapy did not yield a significant survival benefit in older patients with AML;however,this result needs to be confirmed in patients at low risk.Patients with TP53 mutations had a poor prognosis.Multivariate analyses revealed that baseline molecular characteristics,leukocyte count,and comorbidities were more important than treatment intensity in predicting survival among older patients with AML.