重组人促红素治疗白血病患者化疗后贫血的临床研究

Clinical trial of recombinant human erythropoietin in the treatment of anemia after chemotherapy in leukemia patients

目的观察重组人促红素注射剂治疗白血病患者化疗后贫血的临床价值,并探究不同剂量的临床疗效差异。方法将白血病患者化疗后贫血患者随机分为对照组、低剂量组和高剂量组。对照组给予常规治疗(口服琥珀酸亚铁结合饮食调理);低剂量组在对照组治疗的基础上,给予75 U·kg^(-1)重组人促红素治疗,每周3次,皮下注射;高剂量组在对照组治疗的基础上,给予150 U·kg^(-1)重组人促红素治疗,每周3次,皮下注射。3组患者均治疗4周。比较3组患者的临床疗效、贫血相关指标、骨髓基质细胞中丝裂原活化蛋白激酶通路相关蛋白的表达水平、卡氏功能状态(KPS)评分,以及安全性。结果对照组、低剂量组和高剂量组分别入组32、33和33例患者,无患者脱落。治疗后,对照组、低剂量组和高剂量组的总有效率分别为62.50%(20例/32例)、78.79%(26例/33例)和87.88%(29例/33例),对照组与高剂量组比较,在统计学上差异有统计学意义(P<0.05)。治疗后,对照组、低剂量组和高剂量组的血红蛋白水平分别为(108.76±6.82)、(112.43±7.31)和(116.27±7.72)g·L^(-1),红细胞计数分别为(3.08±0.42)×10^(12)、(3.34±0.39)×10^(12)和(3.58±0.45)×10^(12)·L^(-1),血细胞比容分别为0.28±0.05、0.31±0.06和0.35±0.07,磷酸化细胞外调节蛋白激酶1/2蛋白相对表达水平分别为1.12±0.16、1.23±0.17和1.35±0.22,磷酸化应激活化蛋白激酶蛋白相对表达水平分别为0.83±0.13、0.76±0.11和0.69±0.09,p-P38蛋白相对表达水平分别为0.92±0.10、0.86±0.09和0.80±0.09,KPS评分分别为(69.35±6.43)、(72.84±6.62)和(76.35±6.77)分。低、高剂量组的上述指标分别与对照组比较,高剂量组的上述指标与低剂量组比较,在统计学上差异均有统计学意义(均P<0.05)。3组患者的药物不良反应均以皮肤过敏和胃肠道反应为主。对照组、低剂量组和高剂量组的总药物不良反应发生率分别为12.50%、18.18%和18.18%,两两比较,在统计学上差异均无统计学意义(均P>0.05)。结论重组人促红素注射剂可显著纠正白血病患者化疗后贫血,改善患者的健康状况,且150 U·kg^(-1)重组人促红素注射剂的临床疗效显著优于75 U·kg^(-1)。

Objective To observe the clinical value of recombinant human erythropoietin injection in the treatment of anemia after chemotherapy in leukemia patients,and to explore the difference of efficacy of different doses.Methods Patients with anemia complicated by leukemia chemotherapy were selected as the study objects and randomly divided into control group,low-dose group and high-dose group.Patients in the control group received conventional treatment(oral ferrous succinate combined with dietary conditioning),and patients in the low-dose group were given 75 U·kg^(-1)recombinant human erythrophorin treatment on the basis of the control group,subcutaneous injection 3 times a week.High-dose group was treated with 150 U·kg^(-1)recombinant human erythropoietin on the basis of control group,subcutaneous injection 3 times a week.All three groups were treated for 4 weeks.The clinical efficacy,the anemia-related indexes,the expression of mitogen-activated protein kinase path-related proteins in bone marrow stromal cells,Karnofsky performance status(KPS)score and safety of the three groups were compared.Result Control group,low-dose group and high-dose group were enrolled in 32,33 and 33 cases,respectively,without shedding patients.After treatment,the total effective rate of control group,low-dose group and high-dose group were 62.50%(20 cases/32 cases),78.79%(26 cases/33 cases)and 87.88%(29 cases/33 cases),respectively.There was statistical significance in the total effective rate of control group and high-dose group(P<0.05).After treatment,the hemoglobin levels of control group,low-dose group and high-dose group were(108.76±6.82),(112.43±7.31)and(116.27±7.72)g·L^(-1),respectively;red blood cell counts were(3.08±0.42)×10^(12),(3.34±0.39)×10^(12)and(3.58±0.45)×10^(12)·L^(-1),respectively;hematocrit were 0.28±0.05,0.31±0.06 and 0.35±0.07,respectively;the relative expression levels of phosphorylated extracellular regulatory protein kinase 1/2 were 1.12±0.16,1.23±0.17 and 1.35±0.22,respectively;the relative expression levels of phosphorylated stress—activated protein kinase were 0.83±0:13,0.76±0:11 and 0.69±0.09,respectively;the expression levels of p-P38 were 0.92±0.10,0.86±0.09 and 0.80±0.09,respectively;the KPS scores were(69.35±6.43),(72.84±6.62)and(76.35±6.77)points,respectively.The above indexes in the low-dose group and the high-dose group were compared with the control group,respectively,and the above indexes in the high-dose group were compared with the low-dose group,and the differences were statistically significant(all P<0.05).The adverse drug reactions in the three groups were mainly skin allergy and gastrointestinal reactions.The total incidences of adverse drug reactions in the control group,low-dose group and high-dose group was 12.50%,18.18%and 18.18%,respectively,with no statistical significance(all P>0.05).Conclusion Recombinant human erythropoietin can significantly correct chemotherapy related anemia in leukemia,and improve health status,and the curative effect of 150 U·kg^(-1)was better than 75 U·kg^(-1).