Long-term outcomes of autologous stem sell transplantation in severe refractory systemic lupus erythematosus

Cellular Therapy and Transplantation

Boris V. Afanasyev¹  Alexey E. Sizikov¹  Vladimir S. Kozhevnikov¹  Svetlana A. Sizikova¹  Andrey V. Gilevich¹  Igor A. Lisukov¹  Alexander A. Demin¹  Irina V. Kruchkova¹  Lyudmila P. Konenkova¹  Tatyana N. Sentyakova¹  Vladimir A. Kozlov¹  Vera V. Sergeevicheva¹  Alexander D. Kulagin¹  Elena R. Chernykh¹ 

关键词: SLE;    stem cell transplantation;    immune reconstitution;   

DOI  :  10.3205/ctt-2010-No9-abstract02

学科分类：肿瘤学

来源: Universitaetsklinikum Hamburg - Eppendorf / University Medical Center Hamburg - Eppendorf

【 摘 要 】

High-doseimmunosuppressionandautologoushemopoieticstemcelltransplantation(ASCT)hasbeenproposedasaninvestigationaltherapyforpatientswithrefractoryautoimmunediseases.Wereporttheresultsofasingle-centerstudyofASCTin15patients(aged18–55years)withrefractorytostandardimmunosuppressivetreatmentforsystemiclupuserythematosus(SLE)inourInstitutionfrom1998to2009.Methods:Autologoushematopoieticstemcellswerecollectedfrombonemarrow(n=4)ormobilizedfromperipheralbloodwitheithergranulocytecolony-stimulatingfactor(G-CSF)(n=2)orCyandG-CSF(n=9).Pre-transplantconditioningregimensincludedBEAM(n=2),Melphalan140mg/m2+Etoposid1600mg/m2(n=2),Cy200mg/kg(n=3),Cy200mg/kg+ATG(n=2),andCy120mg/kg(n=6).Thecontrolgroupincluded15femalepatients(aged20–55years)withrefractorySLEonstandardimmunosuppressivetreatment.Results:ThreeSLEpatientsdiedduetoearlytransplant-relatedcomplications,and12patientsachievedcomplete/partialremission(CR/PR).Atamedianfollow-upof51±10.,4months,5patientswerestillinCR/PR.Sevenpatients(63.6%)hadrelapsed.Twopatientshadsevereexacerbation(SLEDAIelevationon12points)anddiedat7and8yearsafterASCT.Fivepatientsdevelopedmildexacerbation(SLEDAIelevationon4–11points).Five-yearOSandRFSwere80%and20%.Inthecontrolgroup(medianfollow-up36±7.6months)5-yearnbsp;OSwas70%,CR/PRwas0%,anddiseaserelateddeathwas20%.Completeremissionsobservedinnbsp;SLEpatientsareaccompaniedbyadisappearanceofanti-dsDNAandANAantibodies,increasingnumbersofCD4+CD45RA+Tcells,CD4+CD25+brightTcellsandCD4+Foxp3+cells.WealsodemonstratedthesignificantincreaseofCD4+andCD8+TcellsinS/G2Mphaseofthecellcycleuntil1yearafterASCT.ThisdatademonstratesthatASCTcaninducethehomeostaticproliferationofTcellsandformthebasisforimmunereconstitution.Conclusions:ASCTinrefractorySLEpatientscaninducestablelong-termremissions,however,themajorityofpatient’srelapses.Theassessmentofimmunereconstitutioncanbeimportanttounderstandthemechanismsofre-establishingselftolerance.Internationalclinicaltrialswouldberequiredtoclarifythesequestions.nbsp;

【 授权许可】

Unknown