三尖杉酯碱联合维奈克拉和阿扎胞苷治疗FLT3-ITD突变复发难治急性髓系白血病的研究

张文荟; 裴晓杭; 孔黛; 张萍; 陈香丽; 臧玉柱; 刘忠文

doi:10.16766/j.cnki.issn.1674-4152.003953

三尖杉酯碱联合维奈克拉和阿扎胞苷治疗FLT3-ITD突变复发难治急性髓系白血病的研究

doi: 10.16766/j.cnki.issn.1674-4152.003953

河南省人民医院，郑州大学人民医院血液科，河南郑州 450002

基金项目:

河南省医学科技攻关计划联合共建项目 LHGJ20230016

河南省中青年卫生健康科技创新杰青人才培养项目 JQRC2023014

河南省医学科技攻关计划省部共建重点项目 SBGJ202102041

详细信息

通讯作者:
刘忠文，E-mail: hnsrmyyzy@126.com

中图分类号: R733.7 R730.53
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出版历程
- 收稿日期: 2024-07-22
- 网络出版日期: 2025-06-30

Clinical observations of homoharringtonine with venetoclax and azacitidine in the treatment of FLT3-ITD mutation relapsed/refractory acute myeloid leukemia

Department of Hematology, Henan Provincial People' s Hospital, People' s Hospital of Zhengzhou University, Zhengzhou, Henan 450002, China

摘要

摘要: 目的探讨FLT3-ITD突变复发难治急性髓系白血病(R/R AML)患者接受高三尖杉酯碱联合维奈克拉和阿扎胞苷治疗的效果，评估患者的生存预后水平。方法收集河南省人民医院2018年10月—2024年6月收治的39例确诊FLT3-ITD突变R/R AML患者的病历资料进行回顾性分析。根据患者最终接受的治疗方案进行分组，其中19例接受高三尖杉酯碱+维奈克拉+阿扎胞苷强化疗方案，为观察组；另外20例接受维奈克拉+阿扎胞苷非强化疗方案，为对照组。比较2组短期疗效、生存预后和血液学毒副作用差异。结果 (1) 观察组完全缓解(CR)/未完全恢复(CRi)患者占47.37%(9/19)；对照组形态学CR/CRi患者占20.00%(4/20)，2组比较差异无统计学意义(P＞0.05)；全部患者总缓解率(ORR)为61.54%(24/39)，观察组ORR(73.68%，14/19)高于对照组(50.00%, 10/20)，但组间比较差异无统计学意义(P＞0.05)。(2)观察组无复发生存时间与对照组比较，差异无统计学意义(P＞0.05)；观察组总生存期长于对照组，差异有统计学意义(P＜0.001)。(3)观察组和对照组的血液学毒副作用发生率[68.42%(13/19) vs.55.00%(11/20)]比较，差异无统计学意义(P＞0.05)。结论高三尖杉酯碱+维奈克拉+阿扎胞苷强化疗方案治疗FLT3-ITD突变R/R AML具有良好的短期疗效，可在一定程度上提升患者的生存预后水平，治疗安全性较理想。
- 复发难治急性髓系白血病 /
- FLT3-ITD突变 /
- 强化疗 /
- 高三尖杉酯碱 /
- 维奈克拉 /
- 阿扎胞苷
Abstract: Objective To explore the clinical effects of homoharringtonine with venetoclax and azacitidine in the treatment of FLT3-ITD mutation relapsed/refractory acute myeloid leukemia (R/R AML) and to evaluate the survival and prognosis of patients. Methods Thirty-nine FLT3-ITD mutation R/R AML patients treated from October 2018 to June 2024 in Henan Provincial People' s Hospital were reviewed. According to the different treatment modes, 20 cases of taking the non-intensive chemotherapy (venetoclax and azacitidine) were included in the control group; 19 cases of taking the intensive chemotherapy (homoharringtonine with venetoclax and azacitidine) were included in the observation group. The hepatic and renal function, short-term effects, treatment prognosis, and toxicity were compared. Results (1) In the observation group, complete remission (CR)/ CR with incomplete hematologic recover (CRi) was achieved in 9 out of 19 patients, accounting for 47.37% (9/19) of the total cases in this group; in the control group, CR/CRi was achieved in 4 out of 20 patients, accounting for 20.00% (4/20) of the total cases in this group. The difference between the two groups was not statistically significant (P>0.05). There were no significant between-group differences in the overall response rate [ORR, 73.68% (14/19) vs. 50.00% (10/20), P > 0.05]. (2) The relapse-free survival (RFS) between groups was not significantly different (P > 0.05); the overall survival (OS) in the observation group was longer than the control group, with a statistically significant difference (P < 0.001). (3) There were no significant between-group differences in the haematological toxicity reaction rates [68.42% (13/19) vs. 55.00% (11/20), P > 0.05]. Conclusion Homoharringtonine with venetoclax and azacitidine can improve the short-term effects, treatment prognosis, and safety for FLT3-ITD mutation relapsed/refractory acute myeloid leukemia patients.
- Relapsed/refractory acute myeloid leukemia /
- FLT3-ITD mutation /
- Intensive chemotherapy /
- Homoharringtonine /
- Venetoclax /
- Azacitidine

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表 1 2组FLT3-ITD突变R/R AML患者一般资料比较

Table 1. Comparison of general information between two groups of R/R AML patients with FLT3-ITD mutation

组别	例数	性别(男性/女性，例)	年龄(x±s，岁)	病程(x±s，年)	PS评分(x±s，分)	维奈克拉+阿扎胞苷使用周期(x±s，个)	髓外病变[例(%)]	复杂型染色体核型^c	ELN风险分层(中/高危, 例)	去甲基化药物使用史[例(%)]
观察组	19	14/5	34.44±11.19	2.86±0.84	0.97±0.23	2.13±0.31	2(10.53)	3(15.79)	11/8	12(63.16)
对照组	20	13/7	37.32±12.13	2.95±0.87	1.16±0.37	2.30±0.62	2(10.00)	3(15.00)	10/10	10(50.00)
统计量		0.345^a	0.770^b	0.328^b	1.914^b	1.074^b	0.003^a	0.005^a	0.244^a	0.686^a
P值		0.557	0.446	0.744	0.063	0.290	0.957	0.946	0.621	0.408
注：^a为χ²值，^b为t值。^c复杂染色体核型参照WHO(2017)修订第4版(WHO-HAEM4R)中AML遗传学异常特征定义。

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表 2 2组FLT3-ITD突变R/R AML患者短期疗效比较

Table 2. Comparison of short-term efficacy between two groups of R/R AML patients with FLT3-ITD mutation

组别	例数	CR(例)	CRi(例)	PR(例)	NR(例)	ORR(%)
观察组	19	2	7	5	5	73.68(14/19)
对照组	20	0	4	6	10	50.00(10/20)
注：2组ORR比较，χ²=2.309，P=0.129。

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表 3 2组FLT3-ITD突变R/R AML患者血液学毒副作用比较[例(%)]

Table 3. Comparison of hematological toxicity between two groups of FLT3-ITD mutated R/R AML patients[cases (%)]

组别	例数	4级血液不良反应	皮肤/黏膜出血	总发生
观察组	19	4(21.05)	9(47.37)	13(68.42)
对照组	20	4(20.00)	7(35.00)	11(55.00)
注：2组血液学毒副作用比较，χ²=0.742，P=0.389。

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