脐血造血干细胞移植.ppt

*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,2015-11-29,非血缘脐血移植中脐血的选择及公共脐血库的建设,2,提 纲,UCBT,治疗恶性血液病的现状；,UCBT,中脐血的选择；,sUCBT治疗恶性血液病单中心结果；,公共,脐血库提供的脐血临床移植情况。,造血干细胞移植会议 苏州,3,2015-8-29,Hefei,3,3,造血干细胞移植会议 苏州,4,2015-8-29,Hefei,4,4,2015-5-5,4,造血干细胞移植会议 苏州,5,2015-8-29,Hefei,5,2015-5-5,5,2014/10/18,19th APBMT Congress,5,2014/6/28,造血干细胞移植会议 苏州,6,2015-8-29,Hefei,6,6,2015-5-5,6,2014/10/18,19th APBMT Congress,6,2014/6/28,7,7,7,7,BMDW,：,There are,600,000,cord blood units stored in public banks,worldwide,.,China,has almost,74,000,cord blood units frozen in,8,public cord blood banks for screening and use.,www.bmdw.org/index.php?id=statistics_cordblood,2015-8-29,Hefei,8,8,HSCT in China,The Chinese Medical Association Society of Hematology,Hematopoietic stem cell transplantation group,64 hospitals,N=4418,/year,（,2014,）,20,%,2%,14%,28%,36%,haplo-identical,Auto-,HSCT,Sibling,UPBST,UCBT,HSCT in China,（,2015,年上半年,68,家移植中心,共,2288,例,）,2,提 纲,UCBT治疗恶性血液病的现状；,UCBT中脐血的选择；,sUCBT治疗恶性血液病单中心结果；,公共,脐血库提供的脐血临床移植情况。,The choose,of cord blood in Chinas UCBT cooperative,group,HLA match,（,donor-recipient,）,TNC(10,7,/Kg),CD34(10,5,/Kg),The tubular recovery rate(%),Before frozen,Tubular recovery,Before frozen,Tubular recovery,6/6,2.5,3.0*,2.0,1.2,1.0,80,85,5/6,3.5,4.0*,3.0,1.5,1.2,80,85,4/6,4.0,3.5,5.0*,3.5,3.0,1.8,2.0,1.7,1.8,80,85,*,Europe Eurocord,；,Choose high CFU or CFU-GM umbilical cord blood after confirmation of TNC and CD34 cells.,14,The problems to be aware of for cord blood selection,HLA、TNC、CD34,+,and CFU；,The status of NIMA in cord blood selection;,The role of HLA-Cw mismatched in CBT;,The influence of recipient HLA antibody;,One-unit vs.two-unit Cord Blood;,TRM,OS,PFS,Haematologica.2015 Oct;100(10):1361-70,Better allele-level matching improves transplant-related mortality after double,cord blood,transplantation,N=133,MD Anderson Cancer Center;Case Western Reserve University;Stanford University,Better allele-level matching improves transplant-related mortality after doublecord bloodtransplantation,TRM,TRM,OS,Haematologica.2015 Oct;100(10):1361-70,N=133,MD Anderson Cancer Center;Case Western Reserve University;Stanford University,14,The donor-recipient HLA matched in CB selection,1568 hematological malignancies patients receiving sUCBT were examined for the effect of allele-level matching at HLA-A、B、C、DRB1 on the outcome of transplantation；,Mismatch at 1 or 2 alleles are well tolerated，,mismatch at 5 alleles should be avoided,.,Eapen M et al.Blood,2014,123(1):133-140,The donor-recipient HLA matched in CB selection,3-year NRM,3-year OS,Eapen M et al.Blood,2014,123(1):133-140,15,The status of NIMA in cord blood selection,1121 hematological malignancies patients received sUCBT;1059 received grafts with 5,6/6 HLA match and 79 have NIMA match;,NIMA match improve neutrophil recovery，reduce TRM and tend to lower the post-transplant relapse rate.,van Rood J J et al.Proceedings of the National Academy of Sciences,2009,106(47):19952-19957.,16,The status of NIMA in cord blood selection,van Rood J J et al.Proceedings of the National Academy of Sciences,2009,106(47):19952-19957.,The role of HLA-Cw mismatched in CBT,803 hematological malignancies patients receiving sUCBT；,HLA typing was done with a minimum of intermediate resolution for HLA A、B and C，and at the allele-level for DRB1;,TRM was higher with mismatched at HLA-Cw independently of the effect of HLA-A、B、DRB1.,Eapen M et al.The lancet oncology,2011,12(13):1214-1221.,The role of HLA-Cw mismatched in CBT,Results of multivariate analysis for TRM,Eapen M et al.The lancet oncology,2011,12(13):1214-1221.,14,73 patients receiving dUCBT between 2004 and 2008；,11 patients had DSAs against one CB unit,7 patients had DSAs against both UCB units;,DSAs increased the incidence of graft failure,100-day mortality or relapse,and lower the long-term PFS and OS.,The influence of recipient HLA antibody,The influence of recipient HLA antibody,no DSAs,DSAs against one unit,DSAs against both units,no DSAs,DSAs against one unit,DSAs against both units,PFS,no DSAs,DSAs against both units,Cutler C et al.Blood,2011,118(25):6691-6697.,OS,DSAs against both units,no DSAs,N Engl J Med.2014 Oct 30;371(18):1685-94.,One-unit vs.two-unit Cord Blood Transplantation for hematologic cancers,One-unit:N=108;two-unit:N=112,One-unit vs.two-unit Cord Blood Transplantation for hematologic cancers,N Engl J Med.2014 Oct 30;371(18):1685-94.,One-unit:N=108;two-unit:N=112,2,提 纲,UCBT治疗恶性血液病的现状；,UCBT,中脐血的选择；,sUCBT治疗恶性血液病单中心结果；,公共,脐血库提供的脐血临床移植情况。,25,16,16,sUCBT using intensified myeloablative conditioning regimen without ATG for the treatment of hematologic malignancies,Zimin Sun,Huilan Liu,Liangquan Geng,Baolin Tang,Changcheng Zheng,Xiaoyu Zhu,Juan Tong,Wen Yao,Lei Zhang,Xingbing Wang,Kaiyang Ding,Zuyi Wang,Department of Hematology,Anhui Provincial Hospital,Affiliated to Anhui Medical University,Treatment process of patients through the study,Intensified myeloablative,conditioning,216,Myeloablative conditioning,35,Ara-c/Bu/CY,41,TBI/Ara-c/CY,106,Flu/Bu/CY,69,2011.08,ChiCTR-ONRC-11001430,251 hematological malignancies received sUCBT,From April 2000 December 2014,19th APBMT Congress,The source of umbilical cord blood,Public Bank of UCB,（,251,cases,）,Shanghai 58,；,Guangzhou 57,；,Guangdong 40,；,Beijing 39,；,Sichuan 33,；,Shandong 12,；,Zhejiang 8,；,Tianjin 4,。,2015-8-29,Day,TBI,12Gy(3Gy Bid2d),CY,120mg/kg(60mg/kg.d2d),Ara-C,8g/m2(2g/m,2,q12h2d),G-CSF,5g/kg/d,BCNU,250mg/m,2,CsA 3mg/kg/d,MMF 30 mg/kg/d,TBI/CY/Ara-C CSA and short-course MMF,For lymphoid malignancies or myeloid malignancies patients with age14 years or primary induction failure or no remission after relapse.,-7,-6,-5,-4,-3,-2,-1,0,+1,造血干细胞移植会议 苏州,2015-8-29,Day,BU,12.8mg/kg(0.8mg/kg q6h4d),CY,120mg/kg(60mg/kg.d2d),Flu,120mg/m,2,(30mg/m,2,4d),BCNU,250mg/m,2,CsA 3mg/kg/d,MMF 30 mg/kg/d,BU/CY/Flu CSA and short-course MMF,For lymphoid malignancies patients with age,14 years or prior radiotherapy which would presuppose a high risk of toxicity.,-8,-7,-6,-5,-4,-3,-2,-1,0,+1,造血干细胞移植会议 苏州,31,2015-8-29,2015-5-5,Day,BU,12.8mg/kg(0.8mg/kg q6h4d),CY,120mg/kg(60mg/kg.d2d),Ara-C,8g/m2(2g/m,2,q12h2d),G-CSF,5g/kg/d,BCNU,250mg/m,2,CsA 3mg/kg/d,MMF 30mg/kg/d,BU/CY/Ara-C CSA and short-course MMF,For myeloid malignancies patients with age,14 years or prior radiotherapy which would presuppose a high risk of toxicity,-9,-8,-7,-6,-5,-4,-3,-2,-1,0,+1,32,Day,BU,12.8mg/kg(0.8mg/kg q6h4d),CY,120mg/kg(60mg/kg.d2d),ATG,7.5mg/kg(2.5mg/kg3d,),CsA 3mg/kg/d,MMF 30 mg/kg/d,BU/CY CSA,，,short-course MMF and ATG,-7,-6,-5,-4,-3,-2,-1,0,+1,造血干细胞移植会议 苏州,33,2015-8-29,23,23,Characteristics,Intensified myeloablative conditioning group,N=216,Myeloablative conditioning group,N=35,P,transplantation(years):median(range),13,（,2-46,）,10,（,2-42,）,0.007,Sex:male,（,%,）,139(64.4),26(74.3),0.251,Weight at transplantation(kg):,median(range),41(10-100),27(12-74),0.0001,Underlying disease(n,%),0.158,ALL/lymphoblastic lymphoma,119,（,55.09,）,21,（,60,）,AML,76,（,35.19,）,10,（,28.57,）,CML,11,（,5.09,）,4,（,11.43,）,Others(MDS),10,（,4.63,）,0,（,0,）,Disease status at transplantation,(n,%),0.041,CR2,155,（,71.76,）,29,（,82.86,）,CR2,、,AP,12,（,5.56,）,4,（,11.43,）,NR,、,BC,49,（,22.69,）,2,（,5.71,）,Disease risk at transplantation,(n,%),0.062,Standard risk,69,（,31.94,）,17,（,48.57,）,High risk,147(68.06),18,（,51.43,）,Patient and Transplantation Characteristics,34,Characteristics,Intensified myeloablative conditioning group,N=216,Myeloablative,conditioning group,N=35,P,HLA-A,B,DR (n,%),0.070,6/6,39,（,18.06,）,1,（,2.86,）,5/6,120,（,55.56,）,24,（,68.57,）,4/6,57,（,26.39,）,10,（,28.57,）,ABO compatibility(n,%),0.861,Match,101,（,46.76,）,16,（,45.71,）,Major mismatch,41,（,18.98,）,5,（,14.29,）,Minor mismatch,61,（,28.24,）,12,（,34.29,）,bilmismatch,13,（,6.02,）,2,（,5.71,）,Patient and Transplantation Characteristics,造血干细胞移植会议 苏州,35,2015-8-29,25,25,Characteristics,Intensified myeloablative conditioning group,N=216,Myeloablative,conditioning group,N=35,P,Total nucleated-cell dose infused,median(range)(10,7,/kg),3.9,（1.71-13.74）,4.99（1.94-16.24）,0.0001,Total CD34,+,cell dose infused,median(range)(10,5,/kg),2.14,（0.4-9.89）,2.98（0.99-29.275）,0.0001,CI of Neutrophil engraftment（95%CI）（%）,97.00,（96.95-97.04）,82.81（81.26-84.35),0.000,CI of Platelet engraftment（95%CI）（%）,85.95,（85.82-86.09）,51.79（49.83-53.75),0.003,ANC engraftment(days),median(range),17（11-37）,21(12-39),0.075,Platelet engraftment(days),median(range),37（15-90）,35.5(21-60),0.804,Results,(1),造血干细胞移植会议 苏州,36,2015-8-29,26,26,7,Engraftment,造血干细胞移植会议 苏州,37,Item,Intensified myeloablative conditioning,N=216,Myeloablative conditioning,N=35,P value,PES,，,N,（,%,）,179,（,82.9,）,17,（,48.6,）,0.000,CI of III-IVaGVHD,（,95%CI,）,16.35,（,16.22-16.48,）,13.39,（,13.00-13.78,）,0.528,CI of 2y cGVHD(limited),（,95%CI,）,14.56,（,14.44-14.68,）,17.78,（17.25-18.31),0.844,Blood infection,n,（,%,）,78,（,36.1,）,8,（,22.9,）,0.125,CMV blood infection,n(%),148,（,68.5,）,14,（,40.0,）,0.001,Results(2),All the patients followed up to 07/31/2015,Complications,造血干细胞移植会议 苏州,38,3-year OS and DFS,Results,(3),3-year OS,3-year DFS,All the patients followed up to 07/31/2015,造血干细胞移植会议 苏州,39,2015-8-29,29,29,11,Results (4),Item,20 years,N=154,20-40 years,N=56,40 years N=6,P value,Weight at transplantation:,Median(range)(kg),36,(10-80),59,(43-100),66,（48-80）,0.000,TNC dose infused,median(range)(10,7,/kg),4.3,（1.98-13.74）,3.4,（1.71-6.76）,3.3,（2.12-3.76）,0.000,Total CD34+cell dose infused,median(range)(10,5,/kg),2.4,（0.54-9.89）,1.75,（0.4-4.95）,2.06,（1.21-3.57）,0.000,HLA-A,B,DR (n,%),0.000,6/6,33,(21.4),6,(10.7),0,5/6,93,(60.4),26,(46.4),1,（16.7%）,4/6,28,(18.2),24,(42.9),5,（83.3%）,2015-10-9,40,Engraftment,41,3-year OS and DFS,3-year DFS,3-year OS,3-year DFS,42,不同预处理方案的疗效,3-year OS,3-year DFS,64.2%,65.5%,70.4%,64.2,%,43,Results (5),Characteristics,CR、CP、AP,N=167,NR、BP,N=49,P,Age at transplantation(years):median(range),13,（,2-46,）,10,（,2-42,）,0.343,Sex:male,（,%,）,106(63.5),33(67.3),0.619,Weight at transplantation(kg):,median(range),41(10-100),27(12-74),0.785,Underlying disease(n,%),0.000,ALL/lymphoblastic lymphoma,99,（,59.3,）,20,（40.8）,AML,56,（,33.5,）,20,（40.8）,CML,11,（6.6）,0,（0）,Others(MDS),1,（,0.6,）,9,（18.4）,TNC dose infused,median(range)(10,7,/kg),4.8,（,2.07-13.74,）,3.3,（,1.71-6.76,）,0.757,Total CD34+cell dose infused,median(range)(10,5,/kg),2.53,（,0.54-9.89,）,1.8,（,0.4-5.24,）,0.585,造血干细胞移植会议 苏州,44,33,180d Transplantation-Related Mortality,造血干细胞移植会议 苏州,45,34,2 year Relapse,46,3-year OS and DFS,HLA配型对sUCBT的影响,比较供受者HLA-,A,B,DR6个位点相合，血清学,与,高分辨,两组的植入率、急性GVHD、TRM、复发率、OS；,比较供受者,高分辨,HLA-,A,B,C,DR8个位点,中,4个位点错配,和,HLA-,A,B,C,DR,DQ10,个位点中,5个位点错配,与5个位点和6个位点错配,两组的植入率、急性GVHD、TRM、复发率、OS；,HLA配型对sUCBT的影响,病人来源：2008.5至2015.6，我院采用强化清髓sUCBT治疗恶性血液病患者253例；,供受者血清学6/6个位点相合12例；等位基因相合17例；,供受者采用10个位点基因型,复核174例，其中HLA-A,B,C,DR4/8个和HLA-A,B,C,DR,DQ5/10个位点错配154例，其他20例；,供受者HLA-A,B,DR6个位点相合低分辨与高分辨两组sUCBT治疗恶性血液病疗效,供受者HLA-A,B,DR6个位点相合低分辨与高分辨两组sUCBT治疗恶性血液病疗效,供受者HLA-A,B,DR6个位点相合低分辨与高分辨两组sUCBT治疗恶性血液病疗效,供受者HLA-A,B,DR6个位点相合低分辨与高分辨两组sUCBT治疗恶性血液病疗效,供受者高分辨HLA-A,B,C,DR4/8个和HLA-A,B,C,DR,DQ5/10个位点错配与5/8个和6/10个位点错配两组sUCBT的结果,供受者高分辨HLA-A,B,C,DR4/8个和HLA-A,B,C,DR,DQ5/10个位点错配与5/8个和6/10个位点错配两组sUCBT的结果,供受者高分辨HLA-A,B,C,DR4/8个和HLA-A,B,C,DR,DQ5/10个位点错配与5/8个和6/10个位点错配两组sUCBT的结果,提 纲,UCBT治疗恶性血液病的现状；,UCBT,中脐血的选择；,sUCBT治疗恶性血液病单中心结果；,公共脐血库提供的脐血临床移植情况。,56,资料来源,2006年9月至2014年12月采用强化清髓技术体系UCBT治疗恶性血液病患者216例；,脐血来自7个（8家）国家公共脐血库；,UCBT植入情况,来源,移植例数,植入例数,髓系植入率（%）,上海,50,48,96,广州,39,39,100,广东,37,37,100,北京,37,34,92,四川,31,30,97,山东,12,11,92,浙江,6,6,100,天津,4,4,100,选择脐血的问题,HLA：国际上要求A,B位点低分，DR位点高分；,欧洲多中心的结果：HLA-A,B,Cw,DR,8个位点高分辨，首先要求DR基因点相合，第二Cw位点，其三A位点，如果5/8位点及以上不相合影响OS，不建议使用；,当HLA相合度高，TNC和CD34的值可以下降；,提供高分脐血初筛的脐血库,广东库、北京库、广州库和浙江库；,各脐血库提供资料的情况,能够提供特殊查询，如脐血母亲的HLA配型四川库；,各脐血库提供资料的情况,能够提供小管复苏的脐血库：北京、上海、广东、四川、浙江、广州（2007年后）、天津库；,选择脐血中准备做的工作,受者NIMA在脐血选择中作用；,供受者HLA高分配型错配在移植中作用；,HLA-Cw不合在脐血移植中作用；,受者HLA抗体的影响；,脐血KIR配型在移植中作用,64,The comparison of our technique system with the similar foreign technology,Research,institute,Engraftmen,rate,(%),Neutrophil,engraftment,（,days,）,Platelet,engraftment,（,days,）,TRM,（,%),Infection,Rate,(%),EUROCORD,(2010),88,24,（,4-73,）,38,（,11-253,）,23,-,CIBMTR,(2013),78,20,46,31,-,JCBBN,(2012),78,24,（,11-51,）,-,-,Bacteria:66,Fungus:12,Virus,：,43,COBLT,(2008),79.9,27(11-90),174(21-353),-,Bacteria:77,Fungus:33,Virus:61,NYBC,(2010),74,-,-,-,-,Our research,97.0,17(11-37),37(15-90),19.50,Bacteria:36.3,Virus:68.8,65,Research institute,Relapes,OS,DFS,acute GVHD,cGVHD,EUROCORD,(2010),2ys,：,43%,2ys,：,63%,2ys,：,49%,II-IV,：,12%,10%,CIBMTR,(2013),2ys,：,32%,2ys,：,33%,2ys,：,30%,II-IV,：,27%,24%,JCBBN,(2012),2ys,：,43%,2ys,：,42%,2ys,：,36%,II-IV,：,37%,24%,COBLT,(2008),2ys,：,19.9%,2ys,：,49%,-,II-IV,：,41.9%,20.8%,NYBC,(2010),3ys,：,21%,-,-,II-IV,：,49%,37%,Our research,（,2014,）,2ys,：,15.36%,3ys,：,64.8%,3ys,：,61.6%,II-IV,：,29.87%,14.56%,The comparison of our technique system with the similar foreign technology,小 结,脐血移植技术体系解决了植入延缓和植入不良的问题，并获得很好的OS和生存质量；,脐血库质量体系的建立，提供优质的脐血是提高移植疗效的基础；,临床与脐血库的密切合作、科学研究和交流沟通，才能更好地发展中国的脐血移植工作。,2000.4,2015.,11,Total,811,cases,，,UCBT,452,cases,。,88,86,57,55,105,UCBT in Anhui Provincial Hospital,114,138,Cord blood transplantation,Elizabeth Shpall,ASH 2012 EDUCATION PROGRAM,3879,Cord blood transplantation,Elizabeth Shpall,ASH 2012 EDUCATION PROGRAM,3879,脐带血在临床上的应用,Roura et al.Stem Cell Research&Therapy(2015)6:123,