血液干细胞之临床应用

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1、血液幹細胞之臨床應用與幹細胞庫之管理中國醫藥大學附設醫院醫學研究部林嬌玲102.06.15CharacteristicsofHematopoieticStemCell•Multi-lineagedifferentiation(whiteHSCcells,redcells,platelet)SelfSelf•Self-renewalcapacityRenewalRenewaldifferentiation•AbilitytoreconstitutemyeloablatedpatientHPCdifferentiationHoffb

2、randAV,PettitJE.ClinicalHematology,2nded.Mosby-WolfeThepercentageofCD34+cellindifferentsource•1-3%ofnucleatedcellfractioninbonemarrow(BMT:1960年)•0.1-0.2%inperipheralblood(PBSCT:1980年)：GCSF-mobilization•0.8-1.2%incordblood(CBSCT:1989年)(Yinetal.,1997)History1914:Alexis

3、Carrel:cellsororgansfromanotheronewouldalwaysberecognizedasforeignandthenberejected.1951:LorenzE.et.al.:Radiationprotectioncouldbeconferredbybonemarrowinfusion.(duetofactorinbonemarrowwillstimulatemarrowrecovery).1957:ThomasEDet.al.:1stattemptofBMTinhumanbeings（failu

4、re;HLAwasidentifiedin1960+）1959:ThomasEDet.al.:2ndattemptofBMTinidenticaltwin（hematologicalrecoveryoccurredin2weeks,butleukemiarecurredmonthslater）TypeofHSCTDonorSelectionProcedureAllogeneic:MSD/MUDBMT兄弟姊妹/非親屬Syngeneic:同卵雙胞胎PBSCTAutologousCBSCTT-celldepletedAutologou

5、sHSCT,forWhat?TorescueBMfailureaftercancertherapy:BreastcancerNPCGermcelltumorEwing’ssarcomaNeuroblastomaOsteogenicsarcomaWilmstumorAllogeneicHSCT,forWhat?Toreplaceincorrigiblehematopoieticdefects:•Quantitativedefect:aplastic/Fanconi’sanemia•Qualitativedefect:malign

6、ancy:leukemia/MDS,lymphoma,myelomanon-malignantdiseases:sicklecellanemia,thalassemia,immunodeficiency…HaploidenticalTransplantation:HoffbrandAV,PettitJE.ClinicalHematology,2nded.Mosby-WolfeAllogeneicBMTMajorCausesofFailure:Graftfailure：totalbodyirradiation1200cGyfai

7、ledtoresultinengraftment.GVHD：someformofmatchingbetweendonor&recipientisnecessary.GVHD（graft-vs-hostdisease；移植物抗宿主疾病）•捐贈者之免疫細胞與受贈者器官之排斥反應•最後終因感染或肝、腎功能衰竭或DIC(DisseminatedIntravascularCoagulation，散播性血管內凝固症)而死亡，死亡率高達75－90﹪。•預防方法：1.移植前後給予免疫抑制劑cyclosporine，若仍發生GVHD，則給予高劑量

8、類固醇治療。2.TcellDepletion•若移植後一直沒有GVHD反應→給DLI（DonorLymphocyteInfusion）產生輕微GVHD，癌症細胞才不易復發。TCellDepletionAnti-TcellmonoclonalAbPositives