基于初始抗真菌治疗反应的二级预防在有肺部曲霉菌病史的异基因造血干细胞移植患者中的应用#510152025303540刘启发1，林韧1，孙竞1，肖扬2，聂大年3，张钰1，范志平1，周红升1，江千里1，徐丹1，魏永强1，李益清1*（1.南方医科大学南方医院血液科，广州，510515；2.广州军区总医院血液科，广州，510000；3.中山大学附属孙逸仙纪念医院血液科，广州，510000）摘要：目的：评价有肺部侵袭性曲霉菌感染病史的异基因造血干细胞移植患者采用初始抗真菌治疗有效的药物进行二级预防的效果。方法：共136例患者入组，真菌二级预防的药物采用初始抗真菌有效的药物，包括伊曲康唑24例，伏立康唑74例，卡泊芬净32例，两性霉素B6例。移植前68例患者肺部真菌感染处于稳定状态，48例处于活动状态。结果：二级预防的成功率为91.2%。12例患者移植后发生突破性真菌感染（IFD），无患者因药物不良反应停止预防。不同预防药物组突破性IFD发生率无统计学差异（P=0.667），移植前真菌感染处于活动或稳定状态的患者移植后突破性IFD亦无差异（P=0.080）。3年累计IFD发生率和肺部曲霉菌病复发率分别为30.4%±4.8%和26.4%±4.7%。结论：对于有肺部侵袭性曲霉菌病史的移植患者，基于初始抗真菌治疗反应选择二级预防药物可能有效且安全。活动性肺部曲霉菌感染可能并不增加移植后突破性IFD的发生率。关键词：血液病学；抗真菌预防；侵袭性真菌感染；异基因造血干细胞移植中图分类号：R552;R551.3AntifungalagentsforsecondaryprophylaxisbasedonresponsetoinitialantifungaltherapyinallogeneichematopoieticstemcelltransplantrecipientswithpriorinvasiveaspergillosisLIUQifa1,LINRen1,SUNJing1,XIAOYang2,NIEDanian3,ZHANGYu1,FANZhiping1,ZHOUHongsheng1,JIANGQianli1,XUDan1,WEIYongqiang1,LIYiqing1(1.DepartmentofHematology,NanfangHospital,SouthernMedicalUniversity,Guangzhou,510515;2.DepartmentofHematology,GuangzhouGeneralHospitalofGuangzhouCommand,Guangzhou,510515;3.DepartmentofHematology,SUNYat-senMemorialHospital,SUNYat-senUniversity,Guangzhou,510000)Abstract:Weperformedaprospectivestudytoevaluatetheefficacyandsafetyofsecondaryantifungalprophylaxis(SAP)forpatientswithahistoryofinvasivepulmonaryaspergillosis(IPA)inallogeneichematopoieticstemcelltransplantation(allo-HSCT).Inthisstudy,thechoicesofprophylacticagentsweremadebasedontreatmentresponsetoinitialantifungaltherapy.Onehundredandthirty-sixpatientsundergoingallo-HSCTwithpriorIPAwereenrolledinthismulticenterstudy.TheagentsofSAPincludeditraconazolein24，voriconazolein74，caspofungin基金项目：高等学校博士学科点专项科研基金资助项目(20104433110003)；863项目（2011AA020105）；国家自然科学基金（81000231，81270647，30971300）作者简介：刘启发（1962.12），男，教授，主任医师，主要研究方向：造血干细胞移植.liuqifa@fimmu.com-1-in32andliposomalamphotericinBin6.Eighty-eightpatientshadstableIPAand48hadactiveIPAatthetimeoftransplants.ThesuccessrateofSAPwas91.2%.Twelvepatientsdevelopedbreakthroughinvasivefungaldisease(IFD),andnonediscontinuedantifungalagentsdueto4550556065707580drug-relatedadverseevents.TheincidenceofbreakthroughIFDwasnotdifferentamongthedifferentantifungalagents(P=0.667)andbetweenpatientswithactiveandstableIPA(P=0.080).The3-yearcumulativeincidenceofIFDandIPArelapsewas30.4%±4.8%and26.4%±4.7%,respectively.OurdataindicatethatSAPwithantifungalagentsbasedoninitialantifungaltherapyhasfavorableefficacyandsafetyinallo-HSCTrecipientswithpriorIPA.ActiveIPAmightnotincreasetheriskofbreakthroughIFDaftertransplantation.Keywords:Hematology;antifungalprophylaxis;invasivepulmonaryaspergillosis;allogeneichaematopoieticstemcelltransplantation0引言侵袭性真菌感染（IFD）是异基因造血干细胞移植（al...