内科理论与实践

内科理论与实践 ›› 2022, Vol. 17 ›› Issue (03): 220-226.doi: 10.16138/j.1673-6087.2022.03.009

• 论著 • 上一篇    下一篇

不耐受强化化疗的初治老年急性髓系白血病患者诱导治疗疗效及安全性

罗东凤1, 游建华2, 李啸扬2, 李军民2, 张赟翔2()   

  1. 1.湖南省娄底市中心医院血液内科,湖南 娄底 417000
    2.上海交通大学医学院附属瑞金医院血液科 上海血液学研究所,上海 200025
  • 收稿日期:2021-10-08 出版日期:2022-05-30 发布日期:2022-08-09
  • 通讯作者: 张赟翔 E-mail:zyx12103@rjh.com.cn
  • 基金资助:
    促进市级医院临床技能与临床创新能力三年行动计划项目(16CR1034B)

Study on the efficacy and safety of different induction therapies in newly diagnosed elderly patients with acute myeloid leukemia and intolerance of intensive chemotherapy

LUO Dongfeng1, YOU Jianhua2, LI Xiaoyang2, LI Junmin2, ZHANG Yunxiang2()   

  1. 1. Department of Hematology, Loudi Central Hospital, Loudi 417000, China
    2. Department of Hematology, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Received:2021-10-08 Online:2022-05-30 Published:2022-08-09
  • Contact: ZHANG Yunxiang E-mail:zyx12103@rjh.com.cn

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摘要：

目的：研究和总结综合老年评估筛选出的不耐受强化化疗急性髓系白血病（acute myeloid leukemia,AML）患者的临床特征,评估不同化疗方案对此类患者的疗效和安全性。方法：纳入2018年6月至2021年5月上海交通大学医学院附属瑞金医院收治的120例初发老年AML,筛选出其中52例不耐受强化化疗患者,回顾性分析其临床特征、诱导治疗安全性及缓解情况。结果：不耐受强化化疗患者中位年龄67.5岁,≥75岁的9例。38例（73%）患者至少有1种合并症或既往病史。47例为新发AML,5例为继发性AML。初发骨髓原始细胞比例54%。共50例患者完成了骨髓细胞遗传学及分子生物学评估。染色体核型低危4例,中危25例,高危21例;高危核型中,复杂及单倍体核型共12例。常见基因突变分别为核仁磷酸蛋白1（nucleophosmin 1,NPM1）（19例）、DNA甲基转移酶3A（DNA methyltransferase 3A,DNMT3A）（14例）、Fms-样酪氨酸激酶3-内部串联重复（Fms-related tyrosine kinase 3-internal tandem duplication,FLT3-ITD）（11例）、TET癌基因家族成员2（ten-eleven translocation 2, TET2）（10例）、Runt相关的转录因子1（Runt-related transcription factor 1,RUNX1）（9例）。细胞遗传学与分子生物学危险分层结果显示,中高危组共43例（86%）（高危组29例、中危组14例）。11例患者仅接受支持治疗;41例接受化疗的患者中,25例采用了去甲基化药物（hypomethylation reagent,HMA）联合维奈克拉（venetoclax,VEN）的方案,其他传统诱导方案包括地西他滨联合预激化疗6例,单药HMA4例,减量伊达比星联合阿糖胞苷、预激化疗及小剂量阿糖胞苷方案各2例。HMA+VEN方案缓解率达64.0%,优于传统诱导化疗患者的31.3%（P=0.04）。并且,HMA+VEN治疗组长期生存也显著优于传统化疗及未治疗组（P=0.001）。结论：不耐受强化诱导化疗的老年AML患者具有高龄、合并症复杂、细胞遗传学及分子生物学不良预后因素多的特点。HMA+VEN的新型诱导方案安全性及疗效良好,将成为治疗老年AML患者的重要选择之一。

关键词: 急性髓系白血病, 老年, 诱导治疗, 不耐受强化化疗, 临床疗效

Abstract:

Objective To study and summarize the clinical characteristics of the patients with acute myeloid leukemia (AML) who were intolerant to intensive chemotherapy screened by comprehensive geriatric assessment, and evaluate the efficacy and safety of different chemotherapy regimens for these patients. Methods From June 2018 to May 2021, in a total of 120 patients with newly diagnosed AML in our center, 52 cases screened as intolerance of intensive chemotherapy were selected and their clinical characteristics, induction safety and remission rate were analyzed retrospectively. Results The median age of the selected patients was 67.5 years old, and 9 cases were ≥75 years old. Thirty-eight patients (73%) had previous medical history or at least one comorbidity. Forty-seven cases were de novo AML and 5 cases were secondary AML. 54% cases had bone marrow blasts at the time of diagnose. A total of 50 patients completed cytogenetic and molecular assessment, in which, 4 patients had low-risk karyotypes, 25 patients had intermediate-risk and 21 patients had high-risk karyotypes. Among the high-risk karyotypes, there were 12 cases with complex karyotypes and monosomal karyotypes. The most common gene mutations were nucleophosmin 1(NPM1) (19 cases), DNA methyltransferase 3A (DNMT3A) (14 cases), Fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (11 cases), ten-eleven translocation 2(TET2) (10 cases) and Runt-related transcription factor 1 (RUNX1) (9 cases). The cytogenetic/molecular risk stratification showed that 43 cases had intermediate (14 cases) or high risk (29 cases), which accounted for 86%. Eleven patients received only supportive treatment. Of 41 patients got chemotherapy, 25 cases received a combination treatment of hypomethylation reagent and venetoclax (HMA+VEN). Other traditional induction included decitabine combined with priming chemotherapy (6 cases), demethylation drug (4 cases), and reduced-dose idarubicin combined with cytarabine, priming chemotherapy and low-dose cytarabine (2 cases). The complete remission rate of HMA+VEN regimen reached 64%, which was better than that (31%) in the patients receiving traditional induction chemotherapy (P=0.004). In addition, the long-term survival of the HMA+VEN treatment group was also significantly better than that of traditional chemotherapy and untreated groups(P=0.001). Conclusions The elderly AML patients with intolerance of intensive induction have the characteristics of advanced age, complicated comorbidities, and adverse prognostic factors in cytogenetics and molecular. The new induction treatment of demethylation drugs and venetoclax has a good effect and will become one of the important regimens for elderly AML patients.

Key words: Acute myeloid leukemia, Elderly patients, Induction treatment, Not candidate for intensive chemotherapy, Efficacy

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