环孢素联合重组人促红细胞生成素治疗慢性再生障碍性贫血的疗效评价

目的 比较环孢素(CsA)联合重组人促红细胞生成素(rhEPO)和单用CsA治疗慢性再生障碍性贫血(CAA)的疗效和安全性。方法 回顾性分析2016年1月至2018年6月北京协和医院血液科收治的79例初治CAA患者的临床资料,其中45例采用CsA+ rhEPO治疗,34例仅采用CsA治疗。入选患者使用CsA至少1.5~2.0年,并随访至少1.0年。比较CsA+ rhEPO组和CsA组患者的疗效、不良反应和长期转归,分析可能的疗效影响因素。 结果 CsA+rhEPO组45例患者中,男14例,女31例,中位年龄43(19,73)岁;CsA使用的中位时间为26(12,38)个月,rhEPO使用的中位时间为4(3,6)个月,中位随访时间为24(12,42)个月。CsA组34例患者中,男16例,女18例,中位年龄36(16,85)岁;CsA使用的中位时间为24(12,40)个月,中位随访时间为25(12,40)个月。两组患者治疗前各临床特征比较差异均无统计学意义(P均>0.05)。治疗后6个月,CsA+rhEPO组患者的部分缓解(PR)(53.3%比25.0%;χ²=6.181,P=0.019)和总反应(OR)(55.6%比31.3%;χ²=4.456,P=0.040)均明显高于CsA组,两组的完全缓解(CR)差异无统计学意义(2.2%比6.3%;χ²=0.810,P=0.567);CsA+rhEPO组和CsA组患者在治疗后3、12个月和随访期末的CR、PR及OR差异均无统计学意义(P均>0.05)。 CsA+rhEPO组患者在治疗6个月时的血红蛋白水平明显高于 CsA组[(102.6±24.0)g/L比(90.3±29.1)g/L;t=2.017,P=0.047],在治疗3、12个月及随访期末与 CsA组差异均无统计学意义(P均>0.05)。 rhEPO组11.1%(5/45)的患者出现注射部位疼痛,两组患者在肌酐升高、胆红素轻度升高、转氨酶升高、牙龈轻中度增生、胃肠道反应和肌颤等不良反应方面差异均无统计学意义(P均>0.05)。在随访期内,两组患者的克隆演变率相仿,均无死亡病例。未发现影响rhEPO疗效的临床预测因素。结论 与CsA单药治疗相比,CsA联合rhEPO治疗CAA在6个月时有更高的有效率及血红蛋白水平,两组不良反应无明显差别。

Evaluation of the Efficacy of Cyclosporin A Combined with Recombined Human Erythropoietin in the Treatment of Patients with Chronic Aplastic Anemia

Objective To compare the efficacy and safety of cyclosporin A(CsA)and CsA combined with recombined human erythropoietin(rhEPO)in the treatment of patients with chronic aplastic anemia(CAA).Methods Data of 79 patients with CAA treated at Department of Hematology,PUMC Hospital between January 2016 and June 2018 were collected for retrospective analysis.Forty-five patients were treated with CsA+rhEPO,and the other 34 patients with CsA alone.All the enrolled patients were treated for at least 1.5-2.0 years and followed for at least 1.0 year.The efficacy,side effects,long-term outcomes were compared between the two groups,and factors that may influence the efficacy were analyzed.Results The patients treated with CsA+rhEPO included 14 males and 31 females,with a median age of 43(19,73)years old.The median treatment duration of CsA and rhEPO was 26(12,38)and 4(3,6)months,respectively,and the median followed-up time was 24(12,42)months.The patients treated with CsA alone included 16 males and 18 females,with a median age of 36(16,85)years old.The median CsA treatment duration was 24(12,40)months and the median follow-up time was 25(12,40)months.There was no statistical difference in baseline characteristics between the two groups(all P>0.05).After 6 months of treatment,CsA+rhEPO group had higher overall response(OR)rate(55.6% vs. 31.3%;χ ²=4.456,P=0.040)and partial response(PR)rate(53.3% vs. 25.0%;χ²=6.181,P=0.019)than CsA group,and the complete response(CR)rate showed no statistical difference between the two groups(2.2% vs. 6.3%;χ²=0.810,P=0.567).The CR,PR,and OR rates showed no statistical difference between the two groups after 3 and 12 months of treatment and at the end of follow-up(all P>0.05).Similarly,the hemoglobin level at the sixth month of treatment with CsA+rhEPO was higher than that with CsA alone [(102.6±24.0)g/L vs.(90.3±29.1)g/L;t=2.017,P=0.047].However,it showed no significant difference between the two groups at other time points(all P>0.05).The side effects,including an increase in serum creatinine,slight increase in bilirubin,increase in aminotransferase,mild to moderate gingival hyperplasia,gastrointestinal reaction,and muscular fibrillation,had no significant differences between the two groups(all P>0.05),except that 11.1%(5/45)patients in the CsA+rhEPO group reported soreness at the injection site.The two groups showed similar rates of clonal revolution during the follow-up period and no death.No clinical factor was found for prediction of the efficacy of CsA+rhEPO. Conclusion CsA+rhEPO has higher OR rate and hemoglobin level than CsA alone at the sixth month of treatment,and it has similar side effects compared with CsA alone.