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HongKongMedJVol15No3Supplement3June2009GeneralsurveyBloodandmarrowtransplantation(BMT)inPeople'sRepublicofChina(PRC)hasbeendevelopingsteadilyinthepast10years.
TherehasbeengrowthinthenumberofBMTprocedures,andmoreremarkably,thenumberofBMTunits.
ThetotalnumberofBMTbeingperformedisapproximately2000peryear,including1000allogeneicBMT(allo-BMT)attheendofSeptember2008.
ThedistributionofthenumberperformedinthosemajorBMTunitsisshowninFigure1.
ThetotalnumberofBMTunitsinPRChasincreasedtoabout100,notwithstandingthestrictregulationofauthorisingBMTunitsbythegovernment.
Theincreaseinthenumberofallo-BMTbeingperformedintheyear2008,comparedtothatin1998,however,lagsbehindtheincreaseinthenumberofBMTunits(Fig2).
Thisisbecausethemedicalinsurancecannotsufficientlycovertheruralarea.
Moreover,BMT-relatedmedicalskillandexperience,andtherelatedmedicalandlaboratorysupportrequiredaretremendous.
Hence,patientsareoftengravitatedtohospitalswithbettertrackrecordandmoreexperienceddoctors.
AnadditionalreasonfortheslowingofgrowthinBMTnumberistheuseofimatinibmesylateinpatientswithchronicmyeloidleukaemia(CML).
1Arecentsurveyof12majorBMTunitsindicatesthatpredominanttypesoftransplantationperformedareidenticalsibling(38.
6%),relatedhaploidentical(19.
4%),unrelated(17.
2%),andautologous(24.
5%);andindicationsofdiseaseentitiesbeingtransplantedaremainlyacutemyeloidleukaemia(AML,32.
8%),acutelymphoblasticleukaemia(ALL,20%),CML(18.
9%)andlymphoidmalignancies(13.
5%).
2Statusofallogeneicbloodandmarrowtransplantationfromhumanleukocyteantigen–identicalsiblingorunrelateddonorHumanleukocyteantigen(HLA)–identicalsiblingBMTformsthemajorpartofBMTperformedinPRC.
Althoughfamily,mostlysibling,donorsaremostoftenused,unrelateddonorsfromtheChineseMarrowDonorProgramandfromTaiwanTzuChiStemCellCenterhavebeenincreasinglyused.
Theseunrelateddonors,especiallythosefromBloodandmarrowtransplantationinmainlandChinaSCIENTIFICPAPERKeywordsChina;StemcelltransplantationHongKongMedJ2009;15(Suppl3):9-12DeclarationTheauthorsdidnotreceivegrantsoroutsidefundinginsupportoftheirresearchfororpreparationofthismanuscript.
Theydidnotreceivepaymentsorotherbenefits,oracommitmentoragreementtoprovidesuchbenefitsfromacommercialentity.
PekingUniversityPeople'sHospital;FudanUniversity;BeijingandShanghaiDao-PeiHospital,ChinaDPLuCorrespondenceto:DrDPLuTel:008601088324617Fax:008601068333439E-mail:lscm2@yahoo.
comDPLu陸道培Asof1981,allogeneicbonemarrowtransplantation(allo-BMT)wasappliedinanacuteleukaemiapatientwithsuccess.
Sincethen,thenumberofBMThasbeenincreasinggradually,especiallysincethe1990s.
Approximately2000BMTsperyearhavebeenperformedinrecentyearsinmorethan100BMTunitsinmainlandChina.
Arecentsurveyof12majorBMTunitsindicatesthatthepredominanttypesoftransplantationperformedareidenticalsibling(38.
6%),relatedmismatched/haploidentical(19.
4%),unrelated(17.
2%),andautologous(24.
5%).
Theindicationsofmajordiseaseentitiesareacutemyeloidleukaemia(32.
8%),acutelymphoblasticleukaemia(20%),chronicmyeloidleukaemia(CML)[18.
9%],andlymphoidmalignancy(13.
5%).
Thenumberoftransplantsfromunrelateddonororrelatedmismatched/haploidenticaldonorhasbeenincreasingsignificantlyinrecent6years.
Granulocytecolony-stimulatingfactor–mobilisedbonemarrowplusperipheralbloodareroutinelyusedasasourceofstemcellsforhaploidenticalBMT.
Umbilicalcordbloodisusedlessoften.
Althoughthetotalnumberofpatientswhoreceivedallo-BMTcontinuestoincrease,theincreaseinBMTforCMLhasbeenflattenedsince2004.
Bytheendof2008,morethan960000volunteer'shumanleukocyteantigen(HLA)dataareavailableinChineseMarrowDonorProgram(CMDP),andmorethan1100stemcelldonationshavebeenperformedfromit.
StemcellsforunrelatedBMTinmainlandChinaaremainlyfromTaiwanTzuChiStemCellCenterandCMDP.
RelatedHLA-mismatched/haploidenticalBMThasreachedfairlygoodoutcomesintermsofsevereacutegraft-versus-hostdisease(GVHD),chronicGVHD,relapse,treatment-relatedmortality,disease-freesurvival,andoverallsurvival,whicharecomparablewithHLA-identical-siblingBMTintheauthor'sBMTunits.
SyngeneicBMTstartedsuccessfullyin1964andhasstillverygoodoutcomesinmorethan23BMTunitsfromthestatisticsofChineseSocietyofBloodandMarrowTransplantation.
#Lu#10HongKongMedJVol15No3Supplement3June20091981年異基因骨髓移植(BMT)治療急性白血病在北京獲得成功.
之後,BMT的例數在中國大陸逐漸增加,尤其是上世紀九十年代以後更有長足發展.
近年,中國大陸超過100個BMT中心每年約進行2000例BMT.
最近一項來自12個主要BMT中心移植情況的調查顯示,主要的移植類型有HLA同胞相合移植(38.
6%),親緣部分相合/單倍體相合移植(19.
4%),非血緣移植(17.
2%)及自體移植(24.
5%).
主要的移植適應症包括AML(32.
8%)、ALL(20%)、CML(18.
9%)及淋巴系統惡性腫瘤(13.
5%).
最近6年,非血緣及親緣部分相合/單倍體相合移植的例數明顯增加.
G-CSF動員的骨髓加外周血已作為親緣部分相合/單倍體相合移植的常規造血幹細胞來源.
臍帶血移植應用最少.
雖然白血病進行異基因BMT的例數持續增加,但CML接受BMT的例數自2004年起增加趨勢明顯放緩.
至2008年底,中國造血幹細胞捐獻者資料庫(CMDP)已有960000多份HLA配型資料入庫,實現捐獻1100多例.
大陸非血緣BMT的幹細胞來源主要為臺灣慈濟幹細胞中心和CMDP.
在作者的BMT中心,親緣部分相合/單倍體相合移植在嚴重急性GVHD、慢性GVHD、復發率、治療相關死亡率、無病生存率及總生存率方面均取得了與同胞相合移植相似的結果.
同基因BMT於1964年在北京獲得成功,來自中華造血幹細胞移植協會(CSBMT)的報告顯示多於23個移植中心的同基因BMT的結果仍然非常令人鼓舞.
中國大陸的造血幹細胞移植Taiwan,areverymuchappreciatedbythepatients,whoaredesperatelyinneedofunrelatedBMT.
Theindicationsforallo-BMTaremostlyhaematologicalmalignancies,especiallyAML,ALLwithpoorprognosis,orCMLinacceleratedorblasticphase.
Thegeneraloverallsurvivalisaround75to85%,dependinguponthediseasestagesofthepatients.
ThereisatendencyinPRCthatpatientswithless-advancedorless-complicateddiseasearetreatedin'developing'BMTunits,whilethemoredifficultandchallengingcasesarereferredtomorematureanddevelopedBMTunits.
HaploidenticalbloodandmarrowtransplantationThefirstlarge-scalehaploidenticalBMT(haplo-BMT)programinPRCwasdevelopedbyDrShuquanJi.
3,4Thestemcellusedwasgranulocytecolony-stimulatingfactor(G-CSF)–mobilisedbonemarrow(BM),whileantithymocyteglobulin(ATG)andtotalbodyirradiation(TBI)constitutedtheconditioningregimen.
Areportofhaplo-BMTwithlargernumberofpatients,conditionedwithanon-TBIregimen,wassubsequentlypublishedbyLuetal.
5ThisprotocolstillemployedG-CSFandATG,andwascharacterisedbyprolongedandstrengthenedimmunosuppression,andacombineduseofBMandperipheralblood(PB)assourcesofstemcells.
Therationaleforprolongedimmunosuppressionbeforestemcellinfusionwasbasedontheexperienceofamelioratedgraft-versus-hostdisease(GVHD)followinghaplo-BMTrecipientwithseverecombinedimmunodeficiencydiseasecases.
AcombinationofBMandPBstemcellswasalsofoundtobedesirableforanumberofreasons.
Firstly,theycanprovidemorestemcellsthanasinglesource.
Secondly,mesenchymalcellsandotherstromacellsareharvestedfromtheBM.
Finally,comparedtoasinglestemcellsource,moreimmuno-modulatingcellscanbeobtained.
ThisprotocolwascoinedbythepresentauthorasGIACprotocol,andisusedwidelyinPRC.
6Relatedhaplo-BMThasachievedfairlygoodoutcomesintermsofsevereacuteGVHD(aGVHD),chronicGVHD(cGVHD),relapse,treatment-relatedmortality(TRM),disease-freesurvival(DFS),andoverallsurvivalwhicharecomparablewithHLA-identicalsiblingBMTproceduresperformedinparallelinthesameBMTunit.
ThisachievementwasrecognisedwiththeFirstPrizeoftheBeijingScienceandTechnologyAwardin2006.
MeasuresagainstcomplicationsinbloodandmarrowtransplantationCytotoxicTlymphocytes(CTL)areusedinPRCagainstrefractorycytomegalovirusandEpstein-Barrvirusreactivations/infections.
TheCTLarepreparedincollaborationwiththeUniversityofFlorida(Long-JiChang)andVectoriteBiomedicaInc.
(Taiwan).
Theresultshavebeenencouragingandmightbehelpfulnotonlyinthetreatment,butalsointheprophylaxisofsevereclinicalinfections.
Leukaemiarelapseisalsoamajorcomplication1.
InstituteofHematology,PUPH2.
Dao-PeiHospital3.
307HospitalofPLA4.
XinQiaoHospitalofTMMU5.
ZhejiangUniversity1stHospital6.
JiangsuInstituteofHematology,SU7.
WuhanUnionHospital8.
PekingUniversity1stHospital9.
InstituteofHematology,CAMS10.
301HospitalofPLA11.
NanfangHospital12.
JinanUniversity1stHospital13.
309HospitalofPLA14.
ZhujiangHospital15.
ShanghaiChildren'sMedicalCenter16.
ChanghaiHospitalofShanghai17.
WuhanTongjiHospital18.
304HospitalofPLAFIG1.
Distributionofthenumberofbloodandmarrowtransplantation(BMT)performedinmajorBMTunitsinmainlandChinafromJanuary2008toSeptember2008#BloodandmarrowtransplantationinChina#HongKongMedJVol15No3Supplement3June200911afterBMT.
Theimmunotherapywithdendriticcell–primedcytokine-inducedkillercell(DC-CIK)hasbeenusedinrelapsingpatientsafterallo-BMT.
TheencouragingresultsindicatethatdonorDC-CIKisasafeandeffectivemeansinthetreatmentofearlyleukaemiarecurrenceafterallo-BMT.
Thisisespeciallyusefulforpatientswhohavefailed,orareineligiblefor,immunosuppressantwithdrawal,chemotherapy,anddonorlymphocyteinfusion.
7CordbloodanditsutilityCordbloodbanksforpublicusearedevelopingslowlyinourcountrywithoutfinancialsupportfromthegovernment.
However,duetotherapiddevelopmentofthetwostemcelldonorprogramsinmainlandChinaandTaiwan,aswellasthegrowthofhaplo-BMT,transplantsfromunrelatedcordbloodarelessoftenperformed.
Oneadditionalobstacleistheslowplateletengraftment,translatingtohighercostsassociatedwithmoreplateletinfusionpost-BMT.
Theuseofcordbloodasthird-partyhaematopoieticcellswassuggestedandwidelyusedinourinstitute.
OurgrouppioneeredthepredecessorformofthistreatmentintheusageoffoetalliverandthymuscellstofacilitaterelatedmismatchedBMT.
8Double-cordbloodtransplantwasstartedbytheauthorasearlyas2000.
9-11Itisgratifyingtonotethatthefirsttwopatientswhoreceiveddoublecordbloodtransplantarestillaliveandwell.
OurpreliminaryclinicalstudyhasshownthatusingcordbloodasthethirdpartycellscouldsignificantlyreducetheincidencesofaGVHD(especiallysevereaGVHD)andalsocurtail100-dayTRMinhaplo-BMT.
12Syngeneicbloodandmarrowtransplan-tationSyngeneicBMT(syn-BMT)hasbeenappliedforthetreatmentofmanymalignantornon-malignanthaematologicaldisorders.
ItisassociatedwithinsignificantGVHD,muchlessTRM,andlowerrelapseratescomparedtoautologousBMT.
However,thelimitednumberofcasesperformedineachsingleBMTcentreprecludedmeaningfulstatisticalanalysis.
Toaddressthisissue,theChineseSocietyofBloodandMarrowTransplantation(CSBMT)hadperformedacollaborativesurveyamongtheBMTcentresinCSBMT.
FromJanuary1964toDecember2008,atotalof77syn-BMTswereperformedin23BMTcentres.
Thediagnosisincludedsevereaplasticanaemia(SAA,22cases),AML(23cases),ALL(14cases),CML(9cases),lymphoma(3cases),myelodysplasticsyndrome(4cases),largegranularlymphocytosis(1case),andneuroblastoma(1case).
Mainpre-conditioningregimenswereCY/TBIorBU/CYformalignantdiseases,noneorCY/ATGforSAA.
Themedianfollow-uptimewas32months(1monthto44years).
Allpatientsachievedengraftmentandthreeofthemexperiencedlaterejection.
Of77patients,sixhadgradeItoIIaGVHD.
AllaGVHDwascontrolledwithlow-dosesteroid.
NocGVHDwasnoted.
Notransplant-relateddeathoccurred.
Amongpatientswithnon-malignantdisorders,87%ofcasesachieveddurableDFS.
Thelongestsurvivorisaliveandwell44yearsaftersyn-BMT.
Amongpatientswithmalignantdiseases,69%achieveddisease-freesurvival.
Syn-BMTisasafeandeffectivetherapeuticoptionforbothacquirednon-malignantandmalignanthaematologicdisorders.
Syngeneicdonor,ifavailable,shouldbethefirstchoice.
ConclusionBonemarrowtransplantationhasbeendevelopingcontinuouslyinmainlandChina.
Concurrentdevelopmentswereseeninthefieldsofmatched-siblingBMT,matched-unrelatedBMT,cordbloodbankingandtransplantation,aswellashaplo-BMT.
AdvancedclinicaltechniquessuchasCTLtreatmentforviralcomplications,aswellasspecialprotocolforhaplo-BMTandcordbloodcellsasthethirdpartycellsarebeingdeveloped.
Alongwiththegrowthofeconomyandimprovedscientificresearch,PRCholdsgreatpromiseasanemergingforceinthefieldofBMT.
ItisnaturalthatCSBMTwillplayanimportantroleinthecollaborationandadvancementofBMTamongChineseworldwide.
1998370No.
ofBMTpatientsYear200857077097011701370020406080120100No.
ofBMTunitsNo.
ofBMTpatientsNo.
ofBMTunits710100FIG2.
Increaseinnumberofallogeneicbloodandmarrowtransplantation(allo-BMT)incomparisonwithBMTunitsin10years#Lu#12HongKongMedJVol15No3Supplement3June20091.
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