地西他滨维持治疗对适合强化疗中低危急性髓细胞白血病患者生存的影响

doi:10.3969/j.issn.1004-583X.2025.05.010

摘要/Abstract

摘要：

目的探讨地西他滨维持治疗对适合强化疗中低危急性髓细胞白血病(acute myeloid leukemia, AML)患者生存的影响。方法回顾性分析2017年1月-2024年1月安徽医科大学第二附属医院收治的适合强化疗中低危AML患者107例,根据患者是否接受地西他滨维持治疗意愿分为维持治疗组(n=59)和对照组(n=48)。维持治疗组根据预后分层分为低危组(n=32)和中危组(n=27),根据微小残留病(minimal residual disease, MRD)分为MRD阳性组(n=20)和MRD阴性组(n=39)。维持治疗组给予地西他滨15 mg/(m²·d),静滴,d1~5,为1个疗程,每2个月治疗为1个周期,连续应用6个疗程,对照组仅定期检测。收集并比较患者临床资料,主要观察无复发生存期(relapse-free survival, RFS)和总生存期(overall survival, OS)。结果随访截至2024年10月,维持治疗组和对照组患者中位RFS分别为40个月(95%CI: 11.427~68.573)与19个月(95%CI: 9.085~28.915),中位OS分别为46个月(95%CI: 21.538~70.462)与32个月(95%CI: 19.318~40.682),差异均有统计学意义(P<0.05)。接受维持治疗的低危组与中危组AML患者中位RFS和中位OS差异均无统计学意义(P>0.05)。维持治疗前MRD阳性组中位RFS为23个月(95%CI: 11.712~34.288)、中位OS为28个月(95%CI: 22.336~33.664),而阴性组中位RFS和OS均未达到(P<0.001)。进一步分析维持治疗组地西他滨维持治疗前后细胞免疫功能变化,发现调节T细胞水平下降,CD8⁺T细胞和自然杀伤细胞水平均上升,差异有统计学意义(P<0.05)。结论适合强化疗的中低危AML患者可以通过地西他滨维持治疗延长生存期,同时地西他滨维持治疗可改善AML患者细胞免疫功能。

关键词: 白血病, 髓样, 急性, 微小残留病, 地西他滨, 维持治疗, 预后

Abstract:

Objective To investigate the effect of maintenance therapy with decitabine on the survival of patients with low-to-medium risk of acute myeloid leukemia (AML) and suitable for intensive chemotherapy. Methods A retrospective analysis was performed on 107 patients with low-to-medium risk of AML who were suitable for intensive chemotherapy and admitted in the Second Affiliated Hospital of Anhui Medical University from January 2017 to January 2024. Patients were divided into the maintenance treatment group (n=59) and control group (n=48) according to their willingness to receive maintenance treatment with decitabine. Patients in the maintenance treatment group were subdivided into the low-risk group (n=32) and medium-risk group (n=27) according to the prognosis stratification, or subdivided into the minimal residual disease (MRD)-positive group (n=20) and MRD-negative group (n=39) according to the MRD status. Patients in the maintenance treatment group were given intravenous drips of decitabine 15 mg/m2/d for 5 days per course, with a total of 6 courses after an interval of 2 months. Regular detections were given in the control group. The clinical data were collected and compared, including the relapse-free survival (RFS) and overall survival (OS). Results As of October 2024, the median RFS was 40 months (95%CI: 11.427-68.573) in the maintenance treatment group and 19 months (95%CI: 9.085-28.915) in the control group. The median OS was 46 months (95%CI: 21.538-70.462) in the maintenance treatment group, and 32 months (95%CI: 19.318-40.682) in the control group. The differences in the median RFS and OS were statistically significant between groups (P<0.05). There were no significant differences in the median RFS and OS among AML patients receiving the maintenance treatment between the low-risk group and medium-risk group (P>0.05). The median RFS in the MRD-positive group among AML patients receiving the maintenance treatment was 23 months (95%CI: 11.712-34.288), and the median OS was 28 months (95%CI: 22.336-33.664), while the median RFS and OS in the MRD-negative group did not reach (P<0.001). The changes in cellular immune function of decitabine before and after maintenance treatment were further analyzed. It was found that the level of regulatory T cells significantly decreased, and the level of CD8⁺ T cells and natural killer cells significantly increased (P<0.05). Conclusion AML patients with a low-to-medium risk and suitable for intensive chemotherapy can yield survival benefits from decitabine maintenance therapy, which can improve the cellular immune function.

Key words: leukemia, myeloid, acute, minimal residual disease, decitabine, maintenance therapy, prognosis

中图分类号:

R733.71

赵雅静, 陶千山, 沈元元, 董毅. 地西他滨维持治疗对适合强化疗中低危急性髓细胞白血病患者生存的影响[J]. 临床荟萃, 2025, 40(5): 439-444.

Zhao Yajing, Tao Qianshan, Shen Yuanyuan, Dong Yi. Effect of decitabine maintenance therapy on the survival of patients with low-to-medium risk of acute myeloid leukemia and suitable for intensive therapy[J]. Clinical Focus, 2025, 40(5): 439-444.

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https://lchc.magtechjournal.com/CN/Y2025/V40/I5/439

图/表 9

参考文献 22

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项目	维持治疗组(n=59)	对照组(n=48)	统计值	P值
性别[例(%)]
男女	29(49.2) 30(51.8)	24(50.0) 24(50.0)	χ²=0.087	0.931
预后分层[例(%)]
低危中危	32(54.2) 27(45.8)	22(45.8) 26(54.2)	χ²=0.861	0.389
年龄(岁)	54(14,68)	50(16,69)	Z=0.098	0.922
乳酸脱氢酶(U/L)	323(91,1 625)	291(26,1 426)	Z=0.915	0.362
原始细胞(%)	57.00(15.00,97.00)	56.99(21.50,97.00)	Z=0.030	0.976
血小板计数(×10⁹/L)	40(5,244)	35(1,228)	Z=0.704	0.483
白细胞计数(×10⁹/L)	10.86(0.57,162.00)	15.39(0.80,192.46)	Z=0.487	0.628
血红蛋白(g/L)	75.0(40.0,140.0)	80.5(23.0,141.0)	Z=0.534	0.594

项目	维持治疗组(n=59)	对照组(n=48)	统计值	P值
性别[例(%)]
男女	29(49.2) 30(51.8)	24(50.0) 24(50.0)	χ²=0.087	0.931
预后分层[例(%)]
低危中危	32(54.2) 27(45.8)	22(45.8) 26(54.2)	χ²=0.861	0.389
年龄(岁)	54(14,68)	50(16,69)	Z=0.098	0.922
乳酸脱氢酶(U/L)	323(91,1 625)	291(26,1 426)	Z=0.915	0.362
原始细胞(%)	57.00(15.00,97.00)	56.99(21.50,97.00)	Z=0.030	0.976
血小板计数(×10⁹/L)	40(5,244)	35(1,228)	Z=0.704	0.483
白细胞计数(×10⁹/L)	10.86(0.57,162.00)	15.39(0.80,192.46)	Z=0.487	0.628
血红蛋白(g/L)	75.0(40.0,140.0)	80.5(23.0,141.0)	Z=0.534	0.594

项目	MRD阴性组(n=39)	MRD阳性组(n=20)	统计值	P值
性别[例(%)]
男女	20(51.3) 19(48.7)	10(50.0) 10(50.0)	χ²=0.092	0.926
预后分层[例(%)]
低危中危	26(66.7) 13(33.3)	6(30.0) 14(70.0)	χ²=2.653	0.008
年龄(岁)	50(15,57)	52(14,68)	Z=0.098	0.922
乳酸脱氢酶(U/L)	312(91,1 625)	330(125,1 228)	Z=0.576	0.567
原始细胞(%)	54.00(15.00,96.00)	61.50(21.00,97.00)	Z=0.757	0.452
血小板计数(×10⁹/L)	42(5,244)	36.5(8,171)	Z=0.616	0.540
白细胞计数(×10⁹/L)	13.32(0.57,148.50)	10.75(1.30,162.00)	Z=1.711	0.093
血红蛋白(g/L)	77.0(40.0,133.0)	41.5(40.0,140.0)	Z=0.194	0.847

项目	MRD阴性组(n=39)	MRD阳性组(n=20)	统计值	P值
性别[例(%)]
男女	20(51.3) 19(48.7)	10(50.0) 10(50.0)	χ²=0.092	0.926
预后分层[例(%)]
低危中危	26(66.7) 13(33.3)	6(30.0) 14(70.0)	χ²=2.653	0.008
年龄(岁)	50(15,57)	52(14,68)	Z=0.098	0.922
乳酸脱氢酶(U/L)	312(91,1 625)	330(125,1 228)	Z=0.576	0.567
原始细胞(%)	54.00(15.00,96.00)	61.50(21.00,97.00)	Z=0.757	0.452
血小板计数(×10⁹/L)	42(5,244)	36.5(8,171)	Z=0.616	0.540
白细胞计数(×10⁹/L)	13.32(0.57,148.50)	10.75(1.30,162.00)	Z=1.711	0.093
血红蛋白(g/L)	77.0(40.0,133.0)	41.5(40.0,140.0)	Z=0.194	0.847

项目	维持治疗前	维持治疗后	t值	P值
调节T细胞(%)	6.471±1.692	4.748±2.585	6.023	<0.001
CD8⁺T细胞(个/μl)	395.2±186.64	570.49±457.44	3.178	0.002
NK细胞(个/μl)	126.66±85.20	210.86±172.63	4.219	<0.001