CAJ | 학술논문

目的评价抗胸腺细胞球蛋白(ATG)/抗淋巴细胞球蛋白(ALG)治疗重型再生障碍性贫血(SAA)患者的近期疗效及长期生存情况.方法分析1982年12月至2011年6月接受ATG/ALG治疗的345例SAA患者3个月及6个月疗效,长期随访并应用Kaplan-Meier法分析其5年总生存(OS)率.结果 345例患者中非极重型AA(mSAA) 184例,极重型AA(VSAA)161例.中位随访时间为44.0(0.5~244.0)个月.本组患者3个月及6个月总有效率分别为29.9%及45.4%,mSAA患者3个月及6个月总有效率分别为39.2%和55.6%,显著高于VSAA患者的19.6%和34.0%(P值均<0.01).不同种属来源的ATG/ALG治疗SAA患者疗效间差异无统计学意义,兔源ATG中,德国Fresenius制剂(rATG-F)组3个月(10.6%)和6个月(25.5%)总有效率显著低于法国Sangstat制剂(rATG-S)组(36.6%和56.6%)(P值均<0.01).Kaplan-Meier法估计所有患者5年OS率为61.7%(95% CI 55.4%~68.0%),其中mSAA患者5年OS 率为71.0%(95% CI 62.9%~79.1%),显著高于VSAA患者的50.4%(95% CI 40.1%~60.7%)(P<0.01).2007年后实施治疗的VSAA患者5年OS率为73.7%(95% CI 52.2%~95.2%),与mSAA患者的89.7%(95% CI 79.5%~99.9%)比较差异无统计学意义(P=0.240).接受ATG/ALG联合环孢素(CsA)治疗的患者5年OS率为64.8%(95% CI 57.9%~71.7%),显著高于单用ATG/ALG治疗者[32.6%(95% CI 15.7%~49.5%)](P<0.01).加用重组人G-CSF(rhG-CSF)并不能提高患者5年OS率.rATG-S组患者5年OS率为66.1%(95% CI 55.8%~76.4%),显著高于rATG-F组患者[46.6%(95% CI 35.9%~57.3%)](P<0.01).结论 ①mSAA患者近期及远期疗效均优于VSAA患者,2007年后实施治疗VSAA患者长期生存接近mSAA患者;②rATG-S近期及远期疗效均优于rATG-F;③接受ATG/ALG+CsA治疗患者的5年OS率显著高于单用ATG/ALG治疗患者;④加用rhG-CSF并不能提高SAA患者长期生存率.
목적 평개항흉선세포구단백(ATG)/항림파세포구단백(ALG)치료중형재생장애성빈혈(SAA)환자적근기료효급장기생존정황.방법 분석1982년12월지2011년6월접수ATG/ALG치료적345례SAA환자3개월급6개월료효,장기수방병응용Kaplan-Meier법분석기5년총생존(OS)솔.결과 345례환자중비겁중형AA(mSAA) 184례,겁중형AA(VSAA)161례.중위수방시간위44.0(0.5~244.0)개월.본조환자3개월급6개월총유효솔분별위29.9%급45.4%,mSAA환자3개월급6개월총유효솔분별위39.2%화55.6%,현저고우VSAA환자적19.6%화34.0%(P치균<0.01).불동충속래원적ATG/ALG치료SAA환자료효간차이무통계학의의,토원ATG중,덕국Fresenius제제(rATG-F)조3개월(10.6%)화6개월(25.5%)총유효솔현저저우법국Sangstat제제(rATG-S)조(36.6%화56.6%)(P치균<0.01).Kaplan-Meier법고계소유환자5년OS솔위61.7%(95% CI 55.4%~68.0%),기중mSAA환자5년OS 솔위71.0%(95% CI 62.9%~79.1%),현저고우VSAA환자적50.4%(95% CI 40.1%~60.7%)(P<0.01).2007년후실시치료적VSAA환자5년OS솔위73.7%(95% CI 52.2%~95.2%),여mSAA환자적89.7%(95% CI 79.5%~99.9%)비교차이무통계학의의(P=0.240).접수ATG/ALG연합배포소(CsA)치료적환자5년OS솔위64.8%(95% CI 57.9%~71.7%),현저고우단용ATG/ALG치료자[32.6%(95% CI 15.7%~49.5%)](P<0.01).가용중조인G-CSF(rhG-CSF)병불능제고환자5년OS솔.rATG-S조환자5년OS솔위66.1%(95% CI 55.8%~76.4%),현저고우rATG-F조환자[46.6%(95% CI 35.9%~57.3%)](P<0.01).결론 ①mSAA환자근기급원기료효균우우VSAA환자,2007년후실시치료VSAA환자장기생존접근mSAA환자;②rATG-S근기급원기료효균우우rATG-F;③접수ATG/ALG+CsA치료환자적5년OS솔현저고우단용ATG/ALG치료환자;④가용rhG-CSF병불능제고SAA환자장기생존솔.
Objective To assess the short term curative efficacy and long-term survival outcomes of severe aplastic anemia patients following antithymocyte globulin/lymphoglobulin (ATG/ALG) with or without cyclosporine (CsA). Methods A total of 345 cases hospitalized in our hospital between December 1982 and June 2011 were enrolled into this study. We assessed the response rates 3 and 6 months after ATG/ALG, and estimated the overall survival (OS) by Kaplan-Meier method for this cohort of patients. Results The cohort of 345 patients was routinely followed-up with a median follow-up of 44.0 (range, 0.5-244.0) months. The response rates at 3 and 6 months were 29.9% and 45.4%, respectively. The differences in response rates at both 3 (39.2% vs 19.6%, P<0.01) and 6 months (55.6% vs 34.0%, P<0.01) between 184 non-severe aplastic anemia (mSAA) and 161 very severe aplastic anemia(VSAA) were statistically significant. The response rates among the different ATG preparations were comparative; but 3-(10.6%) and 6-month (25.5%) responses produced by rATG-Fresenius were significantly inferior to those by rATG-Sangstat (36.6% and 56.6%, respectively)(all P<0.01). The 5-year OS was 61.7% (95% CI 55.4%-68.0%) for the entire cohort of patients, and 5-year OS for mSAA patients [71.0% (95% CI 62.9%-79.1%)] was superior to that of VSAA patients [50.4% (95% CI 40.1%-60.7%), P<0.01]; but for the patients treated from 2007, the difference of OS in the last 5 years between VSAA and mSAA was not significant [73.7% (95% CI 52.2%-95.2%) vs 89.7% (95% CI 79.5%-99.9%); P=0.24]. Our study also confirmed the superiority of ATG/ALG+CsA regimen [64.8% (95% CI 57.9%-71.7%)] over ATG/ALG alone [32.6% (95% CI 15.7%-49.5%)] with regard to 5-year OS (P<0.01); but the addition of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to ATG/ALG had no benefit in terms of OS. rATG-S produced significantly better 5-year OS [66.1%(95% CI 55.8%-76.4%)] than rATG-F [46.6% (95% CI 35.9%-57.3%); P<0.01]. Conclusions ① The outcome of mSAA was superior to that of VSAA, but the latter was markedly improved in the last 5 years; ②rATG-F was inferior to rATG-S with regard to 5-year OS; ③Immunosuppressive treatment with ATG/ALG plus CsA was more effective than ATG/ALG alone; ④The addition of rhG-CSF to ATG/ALG had no benefit in terms of OS.