Factors affecting the relapse of non-severe aplastic anemia treated with cyclosporine A
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摘要: 目的分析环孢霉素A(CsA)单药治疗的非重型再生障碍性贫血(NSAA)患者获得疗效后，影响复发的因素。方法回顾性收集2012年10月—2020年11月在北京协和医院就诊并采用标准剂量CsA单药治疗的初治NSAA患者资料，分析获得疗效者基线特征、CsA治疗持续时间、足量使用时间、减量时长等因素对其无复发生存(RFS)的影响。结果共纳入179例患者，男性占45.3%，中位年龄46(14~85)岁。中位CsA使用时间24(6~80)个月。69.3%的患者获得疗效，中位起效时间3(1~39)个月。在中位随访34(8~101)个月内，42.7%患者复发，中位复发时间28(6~59)个月，中位RFS为47个月。单因素分析显示，基线中性粒细胞(Neu)高、CsA治疗持续时间>28个月、CsA足量使用时间>16个月、起效时间>4个月者RFS率更高(P=0.006，0.021，0.019，0.034)；多因素Cox回归分析发现，基线Neu高(P=0.006，HR=1.144)及CsA治疗持续时间>28个月(P=0.019，HR=2.045)是RFS的独立影响因素。结论CsA单药治疗的初治NSAA患者，其初始较高的Neu水平、较长的CsA治疗时间等可能与较低的复发率相关。Abstract: ObjectiveTo analyze the risk factors of relapse after effective treatment by cyclosporine A(CsA) in patients with newly diagnosed non-severe aplastic anemia(NSAA).MethodsData of patients with newly diagnosed NSAA receiving standard-dose CsA monotherapy at Peking Union Medical College Hospital from October 2012 to November 2020 were reviewed. The correlation between relapse-free survival(RFS) and risk factors such as patients' baseline characteristics, total CsA duration, full-dosage CsA duration and CsA taper was analyzed.ResultsA total of 179 patients were enrolled, with 81(45.3%) of males and a median age of 46(14-85) years. The median CsA duration was 24(6-80) months, with 69.3% responded at a median time of 3(1-39) months. During 34(8-101) months' follow-up, 42.7% patients relapsed at a median of 28(6-59) months, making median RFS 47 months. Univariate analysis demonstrated that increased baseline neutrophil count, total CsA duration>28 months, full-dosage CsA duration>16 months and time to response>4 months correlated with higher RFS(P=0.006, 0.021, 0.019 and 0.034, respectively). Multivariate Cox regression analysis showed that only increased baseline neutrophil count(P=0.006, HR=1.144) and total CsA duration>28 months(P=0.019, HR=2.045) were independent risk factors of RFS.ConclusionIncreased level of baseline neutrophils and longer CsA duration may predict lower relapse rate in patients with newly diagnosed NSAA treated with CsA monotherapy.
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Key words:
- aplastic anemia /
- cyclosporine A /
- relapse /
- neutrophil count /
- cyclosporine A treatment duration
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表 1 NSAA患者基线临床特征
临床特征 所有患者(n=179) 年龄/岁 47.0(14.0~85.0) 男：女/例 81：98 Hb/(g·L-1) 84.0(25.0~173.0) Ret/(×109·L-1) 6.3(2.7~10.9) Neu/(×109·L-1) 1.2 (0~7.4) PLT/(×109·L-1) 27.0(2.0~87.0) Fer/(ng·mL-1) 386.5(56.1~7 811.5) ALT/(U·L-1) 17.0(3.0~60.0) SCr/(μmol·L-1) 64.5(37.2~115.3) Dbil/(μmol·L-1) 3.9(1.0~10.1) 
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表 2 CsA起效者基线临床特征与RFS关系
临床特征 获得疗效者(n=124) P 年龄/岁 47.5(14.0~85.0) 0.703 男∶女/例 48∶76 0.436 随访时间/月 38(8~101) 0.434 Hb/(g·L-1) 82(25~163) 0.997 Ret/(×109·L-1) 6.8(2.9~10.9) 0.991 Neu/(×109·L-1) 1.2 (0~7.2) 0.006 PLT/(×109·L-1) 24.5(2.0~81.0) 0.566 Fer/(ng·mL-1) 372(56~2381) 0.662 ALT/(U·L-1) 17(3~58) 0.626 SCr/(μmol·L-1) 63(37~115) 0.879 Dbil/(μmol·L-1) 3.7(1.4~10.1) 0.436 PNH克隆/例 15/84 0.078 染色体及基因异常/例 11/21 0.763 注：分类变量P值由log-rank检验比较组间的RFS差异得出；连续变量P值由单因素Cox回归分析其对RFS的影响显著性得出。
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表 3 CsA治疗持续时间、足量使用时间、减量时长与RFS关系
类别 获得疗效者
(n=124)P CsA治疗持续时间 30(6~80) 0.177 CsA治疗持续时间≤28个月 54.0(43.5) 0.021a) CsA治疗持续时间>28个月 70.0(56.5) 0.003b) CsA足量使用时间 19(2~59) 0.607 CsA足量使用时间≤16个月 48.0(38.7) 0.053a) CsA足量使用时间>16个月 76.0(61.3) 0.019b) CsA减量时长c) 8(0~73) 0.352 CsA减量时长≤2个月 45.0(36.3) 0.138a) CsA减量时长>2个月 79.0(63.7) 0.071b) 注：P值由RFS影响因素的单因素Cox回归分析得出。a)log-rank检验比较；b)Breslow(Generalized Wilcoxon)检验比较；c)CsA未减量记为CsA减量时长=0，纳入CsA减量时长≤2个月组。
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