阿扎胞苷联合维奈克拉治疗老年初治急性髓系白血病的疗效分析

Analysis of Curative Efficacy of Azacitidine Combined with Venetoclax in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

目的分析阿扎胞苷联合Bcl-2抑制剂维奈克拉治疗老年初治急性髓系白血病(acute myeloid leukemia,AML)的临床疗效。方法回顾性分析2020年5月至2023年5月锦州医科大学附属第一医院收治的47例老年初治AML患者的临床资料,47例患者均使用阿扎胞苷联合维奈克拉治疗,观察这47例老年患者的完全缓解(CR)率和血液学完全缓解伴不完全恢复(CRi)率,同时观察47例患者的总体有效率(ORR)及微小残留病灶(MRD)的转阴率,分析影响患者疗效和预后的因素,并评估该方案的安全性。结果全部47例AML患者其中观察到客观反应的共35例,其中达到CR的20例(57.10%),一个疗程即达到完全缓解(CR)的有12例(42.50%),达CRi的有4例(8.50%),达到部分缓解(PR)的有4例(8.50%),47例患者的CR/CRi率为51.00%,ORR为59.50%。在获得CR或者CRi患者中,有17例患者(53.10%)在经过≤2个阿扎胞苷联合维奈克拉的疗程治疗后可达到MRD阴性。另外,根据患者诊断时的FAB分型、年龄、初诊时的白细胞计数、初次治疗前的骨髓原始细胞比例及部分特殊基因突变类型等因素进行预后单因素分析,结果显示年龄≥70岁(r=0.035)、未合并TP53突变(r=0.031)以及合并NPM1伴FLT3-ITD高突变(r=0.043)的患者在经过阿扎胞苷联合维奈克拉的治疗后可获得更好的治疗效果。结论阿扎胞苷联合维奈克拉在老年初诊AML患者中的治疗是安全有效的。患者的年龄、NPM1伴FLT3-ITD高突变及是TP53突变是患者疗效的预测因素,初次治疗前的骨髓原始细胞比例、是否存在TP53突变以及是否达到CR或CRi是影响患者生存的独立危险因素。

Objective To evaluate the clinical efficacy of combining azacitidine with the Bcl-2 inhibitor venetoclax in treating elderly patients with newly diagnosed acute myeloid leukemia(AML).Methods Retrospective analysis was conducted on clinical data from 47 elderly AML patients admitted to the First Affiliated Hospital of Jinzhou Medical University between May 2020 and May 2023.All 47 patients were treated with azacytidine combined with venetoclax.The complete response(CR)rate and hematological complete response with incomplete recovery(CRi)rate of the 47 elderly patients were observed,and the overall response rate(ORR)and the negative conversion rate of minimal residual lesion(MRD)of the 47 patients were observed.The factors affecting the efficacy and prognosis of the patients were analyzed,and the safety of the scheme was evaluated.Results Objective response was observed in 35 of the 47 AML patients,of which 20 cases(57.10%)achieved CR,12 cases(42.50%)achieved complete remission(CR),4 cases(8.50%)achieved CRi,and 4 cases(8.50%)achieved partial remission(PR)within one course of treatment.The CR/CRi rate of 47 patients was 51.00%and ORR was 59.50%.Among patients with CR or CRi,17 patients(53.10%)achieved MRD-negative after≤2 courses of azacitidine combined with venetoclax.In addition,univariate prognostic analysis was performed according to FAB classification,age,white blood cell count at initial diagnosis,proportion of bone marrow original cells before initial treatment,and types of some special gene mutations.The results showed that patients aged≥70 years(r=0.035),with no TP53 mutation(r=0.031),and with NPM1 with a high FLT3-ITD mutation(r=0.043)had a better response when treated with azacytidine in combination with venetoclax.Conclusion Azacytidine combined with venetoclax is safe and effective in the treatment of elderly patients with newly diagnosed AML.Age,high NPM1 with FLT3-ITD mutation,and TP53 mutation were predictors of outcome.The proportion of bone marrow original cells prior to initial treatment,presence or absence of TP53 mutations,and achievement of CR or CRi were independent risk factors for survival.