Efficacy analysis of metformin hydrochloride combined with cyclosporine A-containing regimen in the treatment of 27 cases of aplastic anemia
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摘要: 目的 评估含盐酸二甲双胍联合环孢素A方案治疗难治性再生障碍性贫血(AA)患者获得血液学反应的疗效和安全性。方法 入组2020年1月—2021年12月收治的27例难治性AA患者，所有患者在门诊确诊后均接受含盐酸二甲双胍联合环孢素A口服治疗。在接受治疗后1、3、6、12个月进行临床疗效和不良反应评估，评估主要指标包括血红蛋白、中性粒细胞绝对值、血小板计数及输血依赖等，不良反应评估主要包括低血糖反应、肝肾功能评估等。结果 纳入27例难治性AA患者中，男10例，女17例，年龄14~83岁。治疗前后患者血红蛋白、中性粒细胞绝对值、血小板计数的中位数分别为82 g/L vs 111 g/L、1.48×109/L vs 1.83×109/L、34×109/L vs 46×109/L，差异有统计学意义(P< 0.05)。治疗后1、3、6、12个月评估疗效，分别有19例(70.37%)、20例(74.07%)、22例(81.48%)、24例(88.89%)患者获得血液学反应。用药期间有4例患者出现转氨酶轻度升高，5例患者出现肾功能异常，调整用药方案并加用保肝等药物后恢复正常，所有患者均未出现低血糖反应。结论 初步观察含盐酸二甲双胍联合环孢素A方案治疗难治性AA有效且安全性好，提示含盐酸二甲双胍联合治疗方案可作为潜在的治疗难治性AA的方法之一。Abstract: Objective To evaluate the efficacy and safety of metformin hydrochloride-containing combined with cyclosporine A regimen in patients with refractory aplastic anemia(AA).Methods Twenty-seven patients with refractory AA admitted between January 2020 and December 2021 were included. All patients received oral treatment containing metformin hydrochloride combined with cyclosporine A after outpatient diagnosis. The clinical efficacy and adverse events at 1, 3, 6, and 12 months after receiving treatment were evaluated, with key indicators including hemoglobin, the absolute value of neutrophil, platelets, and transfusion dependence. The assessment of adverse events mainly included hypoglycemic reactions and assessment of liver and kidney function.Results Among the 27 patients with refractory AA, 10 males and 17 females aged from 14 to 83 years old. The median hemoglobin, the absolute value of neutrophil, and the platelet count of the patients before and after treatment were 82 g/L vs 111 g/L, 1.48×109/L vs 1.83×109/L, 34×109/L vs 46×109/L, respectively(P< 0.05). After 1, 3, 6 and 12 months of treatment, 19 cases(70.37%), 20 cases(74.07%), 22 cases(81.48%) and 24 cases(88.89%) achieved hematological response, respectively. Four patients experienced mild elevation of transaminases and five patients experienced renal function abnormalities during the dosing period, which returned to normal after adjustment of the dosing regimen and addition of hepatoprotective and other drugs, and all patients did not experience hypoglycemic reactions.Conclusion Preliminary observations showed that metformin hydrochloride combined with cyclosporine A regimen was effective and safe in the treatment of refractory AA, suggesting that the metformin hydrochloride combination regimen could be one of the potential treatments for refractory AA.
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Key words:
- aplastic anemia /
- metformin hydrochloride /
- therapeutic analysis
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表 1 初诊时SAA和CAA患者基线临床特征比较
M(P25，P75) 临床特征 总例数(27例) SAA患者(9例) CAA患者(18例) P 年龄/岁 36(28，47) 34(28，42) 39(25，47) 0.84 男∶女/例 10∶17 3∶6 7∶11 - 中性粒细胞绝对值/(×109·L-1) 1.48(1.03，2.02) 1.48(0.98，1.60) 1.43(1.08，2.38) 0.30 血红蛋白/(g·L-1) 82.00(65.50，105.50) 60.00(58.00，72.00) 92.00(75.75，123.75) < 0.01 血小板计数/(×109·L-1) 34.00(22.50，61.00) 18.00(8.00，22.00) 47.50(34.75，68.75) < 0.01 红细胞计数/(×1012·L-1) 2.37(1.86，3.20) 1.67(1.55，1.92) 2.93(2.37，3.55) < 0.01 白细胞计数/(×109·L-1) 3.40(2.20，3.96) 3.40(2.19，3.84) 3.38(2.26，4.03) 0.76 
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表 2 27例患者的疗效评价
例(%) 时间 总反应 CR PR NR 治疗后1个月 19(70.37) 2(7.41) 17(62.96) 8(29.63) 治疗后3个月 20(74.07) 5(18.52) 15(55.56) 7(25.93) 治疗后6个月 22(81.48) 5(18.52) 17(62.96) 5(18.52) 治疗后12个月 24(88.89) 5(18.52) 19(70.37) 3(11.11)
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表 3 难治性SAA患者治疗前后实验室指标比较
实验室指标 治疗前 治疗后12个月 P 是否有反应/例(%) < 0.01 无 9(100.0) 1(11.1) 有 0 8(88.9) 输血依赖/例(%) 0.05 无 3(33.3) 8(88.9) 有 6(66.7) 1(11.1) 中性粒细胞绝对值/(×109·L-1) 1.5(1.0，1.6) 1.9(0.9，2.4) 0.17 血红蛋白/(g·L-1) 60.0(58.0，72.0) 100.0(98.0，121.0) < 0.01 血小板计数/(×109·L-1) 18.0(8.0，22.0) 33.0(28.0，37.0) 0.01 红细胞计数/(×1012·L-1) 1.7(1.6，1.9) 2.7(2.6，3.2) < 0.01 白细胞计数/(×109·L-1) 3.4(2.2，3.8) 3.7(2.7，4.6) 0.20
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表 4 难治性CAA患者治疗前后实验室指标比较
实验室指标 治疗前 治疗后12个月 P 是否有反应/例(%) < 0.01 无 18(100.0) 2(11.1) 有 0 16(88.9) 输血依赖/例(%) 1.00 无 17(94.4) 18(100.0) 有 1(5.6) 0 中性粒细胞绝对值/(×109·L-1) 1.4(1.1，2.4) 1.9(1.6，2.7) 0.12 血红蛋白/(g·L-1) 92.0(75.8，123.8) 130.0(107.0，139.8) 0.01 血小板计数/(×109·L-1) 47.5(34.8，68.8) 78.5(45.5，120.5) 0.05 红细胞计数/(×1012·L-1) 2.9(2.4，3.5) 3.8(3.2，4.2) 0.01 白细胞计数/(×109·L-1) 3.4(2.3，4.0) 3.9(3.4，5.2) 0.09
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