重型/极重型再生障碍性贫血患者免疫抑制治疗后早期死亡的临床特征及预测模型构建  

Clinical characteristics and prediction model of early death in severe/very severe aplastic anemia with immunosuppressive therapy

作　　者：陈苗[1] 庄俊玲[1] 杨辰[1] 王为[1] 张炎[1] 张路[1] 赵丹青[1] 冯俊[1] 李剑[1] 周道斌[1] 韩冰[1] Chen Miao;Zhuang Junling;Yang Chen;Wang Wei;Zhang Yan;Zhang Lu;Zhao Danqing;Feng Jun;Li Jian;Zhou Daobin;Han Bing(Department of Hematology,Peking Union Medical College Hospital,Peking Union Medical College&Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院、北京协和医学院北京协和医院血液科,北京100730

出　　处：《中华血液学杂志》2022年第11期916-920,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金(81970106);中国医学科学院医学与健康科技创新工程2021年"揭榜挂帅"项目(CIFMS 2021-I2M-1-003);中央高水平医院临床科研业务费资助项目(2022-PUMCH-C-026)。

摘　　要：目的分析重型/极重型再生障碍性贫血(SAA/VSAA)采用抗胸腺细胞球蛋白(ATG)强化免疫抑制治疗后早期死亡(ED)患者的特征并构建ED的预测模型。方法收集2003年8月至2021年8月期间在北京协和医院接受ATG治疗的232例SAA/VSAA患者临床资料,回顾性分析ED(治疗后90 d内死亡)患者的临床特征、死亡原因,采用Cox比例风险模型筛选影响ED的危险因素并构建预测模型。结果232例SAA/VSAA患者接受ATG治疗,19例(8.2%)发生ED,中位发生时间为24(3~85)d。ED主要原因是感染(84.2%),其次为脑出血(10.5%)。多因素分析显示VSAA(HR=15.359,95%CI 1.935~121.899,P=0.010)、采用泊沙康唑预防真菌感染(HR=0.147,95%CI 0.019~1.133,P=0.066)、外周血淋巴细胞计数(LYM)≤0.5×10^(9)/L(HR=3.386,95%CI 1.123~10.206,P=0.030)、PLT≤5×10^(9)/L(HR=8.939,95%CI 1.948~41.019,P=0.005)为ED的独立影响因素。VSAA、采用泊沙康唑预防真菌感染、LYM≤0.5×10^(9)/L、PLT≤5×10^(9)/L分别赋3、-2、1、2分构建临床预测模型,该积分模型曲线下面积(AUC)为=89.324(95%CI 80.859~97.789),积分≥3分患者发生ED的风险为<3分组的23.1(95%CI 5.3~100.2)倍。结论感染和脑出血导致的ED是SAA/VSAA采用ATG治疗的重要挑战。同时具有VSAA、LYM≤0.5×10^(9)/L、PLT≤5×10^(9)/L且未采用泊沙康唑预防真菌感染患者具有较高的ED发生风险。Objective Early death(ED)characteristics and predictive factors analysis in patients with severe/very severe aplastic anemia(SAA/VSAA)treated with intensive immunosuppression therapy and establish an ED prediction model.Methods The clinical data of 232 patients with SAA/VSAA treated with Antithymocyte immunoglobulin(ATG)at the Peking Union Medical College Hospital from August 2003 to August 2021 were collected.The characteristics and causes of ED within 90 days were analyzed retrospectively.Cox proportional hazards model was used to screen the ED risk factors and build a prediction model.Results Only 19 patients(8.2%)developed ED with a median time of 24(3-85)days among the 232 patients with SAA/VSAA who received ATG treatment.The main cause of ED was infection(84.2%),followed by cerebral hemorrhage(10.5%).Multivariate analysis showed that VSAA(HR=15.359,95%CI 1.935-121.899,P=0.010),fungal infection prevention by posaconazole(HR=0.147,95%CI 0.019-1.133,P=0.066),lymphocyte count(LYM)≤0.5×10^(9)/L(HR=3.386,95%CI 1.123-10.206,P=0.030),and PLT≤5×10^(9)/L(HR=8.939,95%CI 1.948-41.019,P=0.005)were ED’s independent influencing factors.To build a clinical prediction model,VSAA,fungal infection prevention by posaconazole,LYM≤0.5×10^(9)/L,and PLT≤5×10^(9)/L were scored with 3,-2,1,and 2,respectively.The integral model AUC=89.324(95%CI 80.859-97.789).The ED risk in patients with a score≥3 was 23.1(95%CI 5.3-100.2)times that in patients with a score<3.Conclusion ED caused by infection and cerebral hemorrhage is an important challenge for SAA/VSAA to be treated with ATG.VSAA,LYM≤0.5×10^(9)/L,and PLT≤5×10^(9)/L patients who did not use posaconazole to prevent fungal infection had a high ED risk.

关 键 词：贫血 再生障碍性 抗胸腺细胞球蛋白 早期死亡 

分 类 号：R556.5[医药卫生—血液循环系统疾病]