黄芪水煎剂联合地西他滨、CAG方案治疗老年急性髓系白血病的临床研究

张倩倩; 封亚丽; 董雯; 李燕; 肖华; 李晓红; 李静

doi:10.14148/j.issn.1672-0482.2022.0199

黄芪水煎剂联合地西他滨、CAG方案治疗老年急性髓系白血病的临床研究

doi: 10.14148/j.issn.1672-0482.2022.0199

张倩倩^1,,
封亚丽²,
董雯³,
李燕⁴,
肖华⁵,
李晓红¹,
李静^1, ,

1.
河北省中医院血液病科, 河北石家庄 050011
2.
河北省中医院心血管科, 河北石家庄 050011
3.
河北医科大学第一医院血液科, 河北石家庄 050031
4.
河北省人民医院血液科, 河北石家庄 050051
5.
河北医科大学第一医院手术室, 河北石家庄 050031

基金项目:

北京市医学奖励基金会课题项目 YJHYXKYJJ-261

河北省中医药管理局科研计划项目 2018009

详细信息

作者简介:
张倩倩, 女, 主治医师, E-mail: zhangqianqianzq@yeah.net

通讯作者:
李静, 女, 副主任医师, 主要从事血液病研究, E-mail: 15613180016@163.com

中图分类号: R259
计量
- 文章访问数: 214
- HTML全文浏览量: 52
- PDF下载量: 22
- 被引次数: 0
出版历程
- 收稿日期: 2021-09-25
- 网络出版日期: 2022-03-24
- 发布日期: 2022-03-10

Clinical Study on the Treatment of Acute Myeloid Leukemia in the Elderly with the Huangqi Decoction Combined with Decitabine and CAG Regimen

1.
Department of Hematology, Hebei Province Hospital of Chinese Medicine, Shijiazhuang 050011, China
2.
Cardiovascular department, Hebei Province Hospital of Chinese Medicine, Shijiazhuang 050011, China
3.
Department of Hematology, The First Hospital of Hebei Medical University, Shijiazhuang 050031, China
4.
Department of Hematology, Hebei General Hospital, Shijiazhuang 050051, China
5.
Operating Room, The First Hospital of Hebei Medical University, Shijiazhuang 050031, China

摘要

摘要: 目的研究黄芪水煎剂联合地西他滨、CAG方案治疗老年急性髓系白血病(Acute myeloid leukemia，AML)的临床疗效及可能机制。方法将2018年1月至2021年7月河北省中医院收治的132例老年AML住院患者随机分成对照组和治疗组各66例。对照组予地西他滨联合CAG方案治疗，治疗组在对照组治疗基础上加用黄芪水煎剂，疗程均为12个月。治疗后观察2组临床疗效、支持治疗及不良反应发生情况，检测2组患者治疗前后免疫功能指标(CD3⁺、CD4⁺、CD8⁺、IgG、IgA、IgM)及凋亡相关指标(Bcl-2、Bax、Bak、Bcl-xl)mRNA表达水平变化情况。结果治疗后，治疗组总有效率高于对照组(P < 0.01)，支持治疗及不良反应发生率低于对照组(P < 0.05，P < 0.01)；2组患者CD3⁺、CD4⁺、CD8⁺细胞比例及IgG、IgA、IgM水平显著降低(P < 0.01)，治疗组CD3⁺、CD4⁺、CD8⁺细胞比例低于对照组(P < 0.01)；治疗组Bcl-2、Bcl-xl mRNA表达水平显著降低(P < 0.01)，Bax、Bak mRNA表达水平明显升高(P < 0.01)，对照组Bcl-2 mRNA表达水平明显降低(P < 0.01)，Bax mRNA表达水平显著增加(P < 0.01)；治疗组Bcl-2、Bcl-xl mRNA表达水平低于对照组，Bak mRNA表达水平高于对照组(P < 0.01)。Logistic回归分析结果显示：影响老年AML患者预后的独立危险因素主要包括年龄、未使用黄芪水煎剂联合地西他滨治疗、免疫功能低下以及不良反应(P < 0.01)。结论黄芪水煎剂联合地西他滨、CAG方案能显著改善老年AML患者临床疗效，改善机体免疫功能指标，其机制可能与调节凋亡相关因子表达有关。
- 老年急性髓系白血病 /
- 黄芪水煎剂 /
- 地西他滨 /
- CAG方案 /
- 临床疗效
Abstract: OBJECTIVE To study the clinical efficacy and possible mechanism of the additional Huangqi Decoction on treating acute myeloid leukemia (AML) in the elderly. METHODS A total of 132 elderly AML inpatients admitted to Hebei province hospital of Chinese medicine from January 2018 to July 2021 were randomly divided into the control group and the treatment group of 66 cases each. The control group was treated with Decitabine combined with conventional CAG regimen, while the treatment group was given with Huangqi Decoction based on the therapies in the control group. After treatment, we observed the clinical efficacy, supportive treatment, and occurrence of adverse reactions in both groups. In addition, we measured the changes of mRNA expression levels of immune function indexes (CD3⁺, CD4⁺, CD8⁺, IgG, IgA, IgM) and apoptosis-related indexes (Bcl-2, Bax, Bak, Bcl-xl) before and after treatment in the two groups. RESULTS After treatment, the total effective rate of the treatment group was higher than that of the control group (P < 0.01), and the incidence of supportive treatment and adverse reactions was lower than that of the control group (P < 0.05, P < 0.01). The proportion of CD3⁺, CD4⁺ and CD8⁺ cells and the levels of IgG, IgA and IgM in both groups were significantly reduced (P < 0.01), while the proportion of CD3⁺, CD4⁺ and CD8⁺ cells in the treatment group was lower than that of the control group (P < 0.01). In addition, Bcl-2 and Bcl-xl mRNA expression levels were significantly reduced (P < 0.01), but Bax and Bak mRNA expression levels were significantly increased in the treatment group (P < 0.01). In comparison, only Bcl-2 mRNA expression levels were significantly reduced (P < 0.01) and Bax mRNA expression levels were significantly increased in the control group (P < 0.01). On top of that, Bcl-2 and Bcl-xl mRNA expression levels were lower in the treatment group than in the control group, but Bak mRNA expression levels were higher in the treatment group than in the control group (P < 0.01). Logistic regression analysis showed that the independent risk factors affecting the prognosis of elderly AML patients mainly included age, non-use of Huangqi Decoction combined with Decitabine treatment, low immune function, as well as adverse reactions (P < 0.01). CONCLUSION Huangqi Decoction combined with Decitabine and CAG regimen can remarkably improve the clinical efficacy of elderly AML patients and improve the body's immune function indexes. Thus, the mechanism may be related to the regulation of apoptosis-related factor expression.
- elderly patients' acute myeloid leukemia /
- Huangqi Decoction /
- Decitabine /
- CAG regimen /
- clinical efficacy

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表 1 2组基线资料比较(x±s，n=66)

Table 1. Comparison on the general data of both groups (x±s, n=66)

组别	年龄/岁	男	女	病因(原发/继发)	WBC/(×10⁹·L^-1)	HGB/(g·L^-1)	PLT/(×10⁹·L^-1)	原始细胞比例	MICM分型		受教育年限
组别	年龄/岁	男	女	病因(原发/继发)	WBC/(×10⁹·L^-1)	HGB/(g·L^-1)	PLT/(×10⁹·L^-1)	原始细胞比例	M1~M2	M3~M5	受教育年限
治疗组	67.32±5.23	41	25	62/4	44.23±81.42	75.73±22.05	67.32±64.23	0.60±0.24	41	25	11.28±3.25
对照组	67.39±5.25	40	26	59/7	45.01±80.79	76.11±21.47	68.41±64.18	0.58±0.25	39	27	11.42±3.19

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表 2 Bcl-2、Bax、Bak、Bcl-xl引物序列

Table 2. Primer sequences of β-actin, Bcl-2, Bax, Bak and Bcl-xl

基因	引物序列	长度/bp
β-actin	上游引物5'-CTCCATCCTGGCCTCGCTGT-3'	268
	下游引物5'-GCTGTCACCTTCACCGTTCC-3'
Bcl-2	上游引物5'-CTGGTGGACAACATCGA-3'	123
	下游引物5'-GGAGAAATCAAACAGAGGC-3'
Bax	上游引物5'-CTGAGGCGCTCCAGGCACCA-3'	510
	下游引物5'-CTCTTAATGTCACGCGATTTC-3'
Bak	上游引物5'-AGAGCTGTCTGAACTCACGT-3'	380
	下游引物5'-TTACACTGTGCCAGAGCCAT-3'
Bcl-xl	上游引物5'-CTAAACTCCCCTCCCATTCT-3'	146
	下游引物5'-TCCACCCAACCCTTAAACCT-3'

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表 3 2组患者疗效及支持治疗情况比较(x±s, n=66)

Table 3. Comparison on the conditions of treatment outcome and supportive treatment in both groups (x±s, n=66)

组别	临床疗效				支持治疗情况
组别	完全缓解	部分缓解	无缓解	总有效率/%	去白红细胞悬液输注量/U	单采血小板输注量/U
治疗组	40	24	2	96.97^**	5.74±3.20^**	2.06±1.68^**
对照组	34	18	14	78.79	8.01±3.79	3.64±2.01
注: 与对照组相比, χ_总有效率²=10.241, ^{* *}P < 0.01。

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表 4 2组患者治疗前后免疫指标水平比较( x±s, n=66)

Table 4. Comparison on immune index levels of venous blood before and after treatment in both groups (x±s, n=66)

组别	时间	CD3⁺/%	CD4⁺/%	CD8⁺/%	IgG/(g·L^-1)	IgA/(g·L^-1)	IgM/(g·L^-1)
治疗组	治疗前	54.33±6.80	36.01±5.05	28.75±6.27	11.60±2.20	2.29±1.02	1.05±0.23
	治疗后	40.32±5.18^**##	28.41±4.71^**##	22.44±5.02^**##	9.22±1.75^**	1.66±0.88^**	0.82±0.24^**
对照组	治疗前	54.12±6.80	35.97±5.02	28.81±6.29	11.64±2.01	2.24±1.10	1.02±0.25
	治疗后	44.08±7.73^**	32.08±5.80^**	25.40±4.88^**	9.32±1.79^**	1.72±0.93^**	0.84±0.32^**
注: 与治疗前比较, ^{* *}P < 0.01;与对照组比较, ^##P < 0.01。

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表 5 2组患者治疗前后Bcl-2、Bax、Bak、Bcl-xl mRNA表达水平比较(x±s，n=66)

Table 5. Comparison on mRNA expression levels of Bcl-2, Bax, Bak and Bcl-xl in bone marrow cells of patients in both groups before and after treatment (x±s, n=66)

组别	时间	Bcl-2	Bax	Bak	Bcl-xl
治疗组	治疗前	1.30±0.20	0.86±0.14	0.73±0.24	1.05±0.12
	治疗后	0.92±0.17^**##	1.02±0.17^**	0.93±0.22^**##	0.90±0.15^**##
对照组	治疗前	1.29±0.21	0.88±0.14	0.71±0.23	1.05±0.14
	治疗后	1.12±0.13^**	1.04±0.22^**	0.70±0.22	1.01±0.12
注: 与治疗前比较, ^{* *}P < 0.01;与对照组比较, ^##P < 0.01。

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表 6 2组患者不良反应发生情况比较(n=66)

Table 6. Comparison on the occurrence of adverse reactions in both groups (n=66)

组别	血小板减少	恶心呕吐	心力衰竭	脱发	肺部感染	发热
治疗组	2^*	2^**	1^*	0^*	2^*	3^*
对照组	9	12	7	4	10	11
注: 2组比较, χ_{血小板减少}²=4.860，χ_恶心呕吐²=7.990，χ_心力衰竭²=4.790，χ_脱发²=4.125，χ_肺部感染²=5.867，χ_发热²=5.114，^P < 0.05，^{ *}P < 0.01。

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表 7 影响老年AML患者预后的Logistic回归分析

Table 7. Logistic regression analysis of the factors affecting the prognosis of elderly AML patients

危险因素	回归系数	标准误	P值	OR值	95%CI
年龄	4.209	2.874	0.001	1.103	1.002~20.719
未联合黄芪水煎剂(地西他滨合并CAG方案)	4.491	3.106	0.000	1.711	1.151~11.092
免疫功能低下	6.052	4.283	0.000	2.384	1.210~7.187
不良反应	5.035	3.952	0.000	1.032	1.014~3.486

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