伴血小板无效输注的重型再生障碍性贫血患者免疫抑制治疗后转归研究  

Prognosis of severe aplastic anemia patients with platelet transfusion refractory following immunosuppressive therapy

作　　者：王世充 葛美丽 李星鑫 邵英起 黄金波 霍佳莉 任翔 张静 王敏 聂能 金朋 郑以州 WANG Shi-chong;GE Mei-li;LI Xing-xin;SHAO Ying-qi;HUANG Jin-bo;HUO Jia-li;REN Xiang;ZHANG Jing;WANG Min;NIE Neng;JIN Peng;ZHENG Yi-zhou(State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China)

机构地区：[1]中国医学科学院血液病医院(中国医学科学院血液学研究所)实验血液学国家重点实验室国家血液系统疾病临床医学研究中心细胞生态海河实验室,天津300020

出　　处：《中国实用内科杂志》2022年第7期557-562,567,共7页Chinese Journal of Practical Internal Medicine

基　　金：国家自然科学基金(81770119)。

摘　　要：目的探讨合并血小板无效输注(platelet transfusion refractory,PTR)的重型再生障碍性贫血(severe aplastic anemia,SAA)患者的临床特征及免疫抑制治疗(immunosuppressive therapy,IST)后转归。方法回顾性分析2011年1月至2020年12月在中国医学科学院血液病医院接受IST的281例SAA的临床资料。分析PTR的SAA患者(PTRSAA)与非PTR患者的临床特征、治疗疗效与长期生存。结果发生PTR患者20例(7.1%)。PTR-SAA患者中极重型再生障碍性贫血(VSAA)(70.0%)居多,明显高于非PTR患者(46.4%)(P=0.04)。PTR-SAA中伴有阵发性睡眠性血红蛋白尿症(PNH)克隆的比例(40.0%)亦明显高于非PTR患者(14.9%)(P=0.004)。PTR-SAA患者起病时血小板(PLT)(3.0×10^(9)/L)及绝对中性粒细胞计数(ANC)(0.14×109/L)均明显低于非PTR患者(10.0×10^(9)/L和0.27×10^(9)/L,P<0.001和P=0.04)。20例PTR患者的中位24 h校正血小板增高指数值(corrected count increment,CCI)为594×109/L。18例PTR-SAA患者完成胸腺细胞球蛋白(ATG)治疗,且ATG后PTR状态均得到改善。PTR-SAA患者的3个月和6个月有效率分别为27.8%和44.4%,均低于非PTR患者(分别为49.2%和60.7%),然而差异无统计学意义。年龄>40岁(OR 2.1,95%CI 1.1~4.1,P=0.02)和VSAA(OR 3.1,95%CI 1.9~5.3,P<0.001)为影响6个月疗效的独立不良预后因素。PTR-SAA患者的10年预估OS为60.9%,明显低于非PTR患者(80.0%,P=0.03)。在VSAA患者中,PTR患者的10年总生存时间(OS)仍显著低于非PTR患者(45.7%比73.0%,P=0.02)。疾病严重程度(SAA)、短病程(≤50 d)为提示生存的良好因素(OR 2.7,95%CI 1.4~4.9,P=0.002;OR 1.9,95%CI 1.1~3.3,P=0.02)。结论PTR-SAA为一种特殊类型的SAA,临床预后相对不良。适当的桥接治疗可使多数患者顺利完成ATG。ATG治疗可有效改善PTR状态,高达近半数的PTR-SAA患者获得基本治愈。Objective To analysis the clinical features of severe aplastic anemia(SAA)patients with platelet transfusion refractory(PTR-SAA)and evaluate the hematological response and survival prognosis of these patients following immunosuppressive therapy(IST).Methods From January 2011 to December 2020,acohort of 281 SAA patients in Institute of Hematology&Blood Diseases Hospital following antithymocyte/lymphocyte globulin(ATG)-based IST were enrolled in this study.We collected their clinical data and retrospectively analyzed theirhematological response rates and long-term survival.Results Twenty patients developed PTR.Very severe aplastic anemia accounted for 70%of PTR-SAA patients,which was significantly higher than that in patients without PTR(46.4%,P=0.04).Additionally,PNH clones presented in up to 40%PTR-SAA patients,which was remarkedly higher than that in patients without PTR.At the onset of disease,the platelet counts(PLT)and absolute neutrophil counts(ANC)were much lower in PTR-SAA than those in patients without PTR(P<0.001 and P=0.04,respectively).The median 24 h corrected count increment(CCI)was 594×10^(9)/L.Eighteen patients safely accomplished the ATG course.What’s more,the status of PTR was corrected in all patients after ATG.The response rates at 3 months and 6 months after ATG were 27.8%and 44.4%in PTR-SAA patients,which were lower than those in patients without PTR(49.2%and 60.7%,respectively)but without significant difference.Older(>40ages)and VSAA patients had inferior response rates at 3 and 6 months than those younger and SAA patients(P=0.02 and P<0.001).The 10-year overall survival(OS)was 60.9%which was significantly lower than that in patients without PTR(80.0%,P=0.03).Multivariate analysis revealed that SAA but not VSAA and short interval from diagnosis to IST(<50days)were positive prognostic factor for OS(OR 2.7,95%CI 1.4-4.9,P=0.002;OR 1.9,95%CI 1.1-3.3,P=0.02).Conclusions PTR-SAA was a special subtype of SAA with a relatively poor prognosis.Adequate therapy targeting PTR could bridge SAA patien

关 键 词：再生障碍性贫血 免疫抑制治疗 血小板无效输注 

分 类 号：R551[医药卫生—血液循环系统疾病]