非清髓性異基因造血干細(xì)胞移植治療惡性血液病26例

1、非清髓性異基因造血干細(xì)胞移植治療惡性血液病26例蘇麗萍，許蓮蓉，姜波，葉芳，朱秋娟，鹿育晉，崔月娥，朱鐳，張麗，馬香蘭【摘要】為研究非清髓性異基因造血干細(xì)胞移植nn-yelablativeallgenEisteelltransplantatin，all-NST治療惡性血液病的療效及相干技能，選擇26例惡性血液病患者作為研究工具急性白血病10例，慢性髓性白血病14例，多發(fā)性骨髓瘤2例，此中14例接納FAfludarabin+ATG+y)預(yù)處置懲罰，12例接納Aelfalan/aleran+ATG+y)預(yù)處置懲罰；用G-SF600g/d或G-SF300g/d+G-SF300g/d舉行外周血干細(xì)胞發(fā)

2、動(dòng)，于第5天開(kāi)始用beSpetra血細(xì)胞分散機(jī)一連網(wǎng)羅2-3次；用環(huán)孢菌素A團(tuán)結(jié)短程甲氨蝶呤防范GVHD；移植后第4周開(kāi)始供體淋巴細(xì)胞輸注，首劑1107/kg，之后根據(jù)臨床反響及嵌合體形成環(huán)境，每4周1次，劑量逐級(jí)遞增；微衛(wèi)星短串聯(lián)重復(fù)序列STR闡發(fā)、Br/Abl交融基因、Ph染色體、HLA位點(diǎn)闡發(fā)、性染色體及AB血型等為植活檢測(cè)指標(biāo)。效果表現(xiàn)：植入率84.62%，aGVHD產(chǎn)生率11.54%，GVHD產(chǎn)生率23.07%；熏染和出血等毒副反響產(chǎn)生率低、反響輕。結(jié)論：非清髓性異基因造血干細(xì)胞移植治療惡性血液病療效確切，毒副作用小，但相干技能，如順應(yīng)癥的選擇、預(yù)處置懲罰方案、移植歷程中的免疫治療等

3、必要進(jìn)一步深化研究?！娟P(guān)鍵詞】造血干細(xì)胞移植；非清髓性異基因造血干細(xì)胞移植；惡性血液病NnyelablativeAllgeneiHeatpietiSteellTransplantatinin26asesfHeatlgialalignaniesKeyrdsheatpietisteelltransplantatin;nnyelablativeallgeneiheatptetisteelltransplantatin;heatlgialalignanyAsnventinalallgeneiheatpietisteelltransplantatin(HST)frpatientsithheatlgial

4、alignaniesbtheradiatesthepatientsunderlyingdiseasesandsuppressestheiriunerespnses，theydntrejetthesubsequentallgrafts.Theallgraftsservet“resuepatientsfrthearrlethaleffetsfthenditiningregiens.nsequently，thenditiningtherapyintensityuldbeliitednlybytxiitiestnn-arrrgans，suhasgut，lung，kidney，heart，andlive

5、r.Thesetxiitieshaverestri-tedHSTtyunger，ediallyfitpatients，ithtreatentadinisteredinspeializedhspitalards.AlstnallgeneiHSThavebeenarriedutinpatients60yearsld，andinnlyafepatientslderthan50years.Sineedianagesatdiagnsesfpatientsithauteyelytileukeias(AL)，hrniyelytileukeias(L)，hrnilyphytileukeias(LL)，nn-H

6、dgkinlyphas(NHL)，andultipleyelas()rangefr65-70years，sthatnventinalallgeneiHSTbenefitnlyainrityfpatientsithandidatedisease.Nnyelablativeallgeneisteelltransplantatin(NST)asfirstdesribedandappliedin1997byGiraltandlleages1-3.Beauseftheirltxiity，nnyelablativeallgeneisteelltransplantatinshsaprisetreduethe

7、rbidityandrtalityassiatedithnventinalhigh-dseheraditherapyandallsallgeneitransplantsinelderlyrediallyinfirpatientsharenteligiblefrnventinalyelablativeHST.Sithasbeeninreasinglyexplredasasafealternativetnventinalhigh-dsetransplantatinregiens.eanalyzedNSTithitsadaptatin，nditiningregien，engraftent，iunth

8、erapyandpliatins，suhasGVHD，indetailsin26patientsithheatlgialalignanieshunderentNSTfrSepteber1998tSepteber2002.aterialsandethdsPatientharateristisPatientstatusbefretransplantatinLabratryparaetersSeruytegalvirus(V)-Igantibdyasdeterinedbyenzyelinkediunsrbentassay(ELISA)，seruV-DNAasdetetedbyplyerasehain

9、reatin(PR)insepatientsandtheresultserenegative.HBsAg，HBeAgandHBAbtestserepsitiveinlpatient，HBeAbandHBAbtestserepsitivein2patients.Huanleukyteantigen(HLA)-identifiatinasarriedutbyserlgialexainatinfrlassIandPR-SSPfrlass.DnrThednrsere13alesand13feales，agerangedfr22t52years(edian38).Alldnrseresiblingbut

10、1asthepatientsfather.utfthesednrs，1aspsitiveinHBsAg，HBeAbandHBAb.17dnrsereHLA-identialathed，4eresinglelusisathed，4eretliisathed，1asthreeli-isathed.11erethesaeABbldtypeand15eredifferent(7ajrinpatible，8inrinpatible).ethdsftransplantatin1patientastreatedbybnearrtransplantatin，7reeivedperipheralbldsteel

11、ltransplantatinbiningithbnearrtransplantatin，18underentperipheralbldsteelltransplantatin.bilizatin，separatinandlletinfperipheralbldsteell(1)G-SF300g，s.tiedaily;(2)G-SF300gplusG-SF300g，s.neaday.lletinstartedfrthefifthdayfbilizatinithbldellseparatr(leukapheresis)knnasbeSpetrafr2-3ties.NuberfNandD34+el

12、lsinfusedThenuberfnnulearells(N)as(4.15-16.28)108/kgfreipenteight(edian，6.872.93108/kg).ThenuberfD34+ellsdeterinedbyflytetryas(3.62-19.32)106/kg(edian，5.054.3106/kg).nditiningregien(1)14patientsreeivedfludarabin50g/dfr5nseutivedays(day9t5pre-transplantatin)，anti-Tlyphyteglbulin(ATG)10g/(kgd)fr4nseut

13、ivedays(day7t4pre-transplantatin)，ylphsphaide30g/(kgd)nday4t3pre-transplantatin3;(2)12patientsunderentelphalan/busulfan2g/(kgd)nday8t5pre-transplantatin，ATG10g/(kgd)ndays7t4pre-transplantatin(24patientsreeivedtheprdutsfuhanInstitutefbilgialpreparatins，2eretreatedithITIX-SANGSTATadeinFrane)，ylphsphai

14、de30g/(kgd)nday4t3pre-transplantatin.Dnrlyphyteinfusin(DLI)4-524patientsereeligiblefrDLIgivenneevery4eeksingradedinresentsardingtthehierifratinandlinialreatin.Generally，thedsefthefirstinfusinas1107/kgin4theekpst-transplantatin.2patientsunderentdnrsteellinfusin(DSI，dnrsperipheralbldsteellinfusin)alsn

15、eevery4eeksingradedinresentsithfirstinfusinf1107/kg.Allpatientsneedtbeinfusedregularlyfr2-3ties.Effiayassay(1)Shrttanderepeats(STRs)6assayasnday10and28pst-transplant，flledneanth;(2)HLA-lusanalysis;(3)br/ablfusingeneandPhiladephiahrsefrLpatientsbinthlyrtrinthly;(4)Sexhrse;(5)ABbldtype.Fll-upPatientse

16、reregularlyflled-upaftertransplantatintassessdiseaserespnseandreissinstatus.TNveber2002，thefll-uptieas1ntht30nths(edian，21nths).Uptn，13patientsarestillindisease-freesurvival.ResultsSideeffetsfheatpietisysteandrenstitutinfheatpietifuntinEngraftentTenty-tpatients(84.62%)ereengrafted，inludingL-P1(n=10)

17、，L-P2(n=2)，ALL-R1(n=2)，2a(n=2)，4a-R1(n=l)，5a-R1(n=3)，(n=2)，hhaddnr-DNAfr20%t100%detetedbySTRsn1nthpst-transplantatin，ith18patientsbEingfulldnrhieris(FD)uptn.fthesepatients，15asesereHLA-athed(88.24%)，4aseseresingle-lusisathed(100%)，3aseseret-li-isathed(75%).4patientsfailedtbeengrafted，inludingALL-R1(

18、n=l)hasHLA-athed，L-B(n=l)hasalsHLA-athed，2a-R2(n=l)hsesteellserednatedbyhisfatheriththree-liisathed，L-P1(n=l)hast-lusisathed.GVHDaftertransplantatinbeausefstppingralsAfr2eeks.Herespndedprptlythigh-dseethyl-prednislne，butdiedfprgressivedyspneaafter24hurs.AllthreepatientsereHLA-athed，hsednrserefeales，

19、inpartiular，thelasttere50and46yearsldrespetively.GVHDurredainlynskinandusain6patients(23.07%)psedf2transfredfraGVHD，L-P1(n=1)，L-P2(n=l)，4a-R1(n=l)andB-ALL-R1(n=l)，utfhihaGVHDf1patienturredinliverandantherinbulbarnjuntiva.utfthelast4patients，3asesreeivedFAnditiningregienand1A，3asesereHLA-athedand1ass

20、ingle-lusisathed，hsednrsere2alesand2feales.InfetiuspliatinsStaphylusaureusinfetinurredbyatheterin1patient，pulnarystaphylusaureusinfetinurredin2，allthestrainsfstaphylusaureusaresensitivetantibitisanderentrlledbythe.nepatientsufferedfrfrequentituritin，urgenyfurinatinandurdynia，ithseverehypereia，edea，b

21、ladderntraturebservedbyystspyandVnegativeinseruandurine.Frtunately，thesesyptsererelievedbyintravenuskenaiand-glbulin.Antherpatientdiedfasphyxian9nthspst-transplantatinbeausefslightinterstitialpneuniaevidenedfthraiTithVnegativeinseru，urine，sputubutnsensitivitytkenai，ganilviranddasansu.TransfusinPlate

22、letslessthan20109/Ldidnturin11patientshneednplatelettransfusin.pliatinsfDLInepatientasresuedfrautedysheatpiesisbyytkinesafterfirstDLI，andthetherhadaGVHDinliverafterfirstDLI.Disussinurstudyshedthat(1)theengraftentfthseinunstablestatusasler.20patientsinstablephase，2ithL-P2ereallsignifiantlyengrafted(P

23、=0.014);(2)theengraftentfthset-liisathedasaslas75%.Hever，singlelusisathedhadfeeffetsntheengraftentthatas100%fengraftentasparedithHLA-athedpatients(P=l.000，0.489，respetively);(3)theagesfdnrsandreipientshadnapparenteffetntheengraftent(P=1.000);(4)thereasnsignifiantdiffereneinengraftentbeteentheFAgrupsandtheAgrups(P=0.306).ThereasnrearkablevariatinintheinidenefGVHDbeteentnditininggrups(P=0.391)，denstratingthatNSTayreduethedif