异基因造血干细胞移植治疗多发性骨髓瘤.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Allogeneic,haematopoietic,cell transplantation for multiple,myeloma,The,allogeneic,transplant has the advantage over the,autologous,transplant,The graft does not contain tumor cells and the potential for a graft versus,myeloma,(,GvM,)effect,Bone marrow transplantation in three patients with multiple,myeloma,Gahrton,G,Ringdn,O,Lnnqvist,B,Lindquist R,Ljungman,P,.,Acta,Med Scand 1986;219(5):523-7.,瑞典卡罗林斯卡医学院,1983,Myeloablative,conditioning,Three patients with multiple,myeloma,received bone marrow grafts from HLA-identical sibling donors,One of the patients,with,IgA,kappa,myeloma,refractory to,alkeran,-prednisone therapy,is well and still without sign of disease 26 months post transplantation,A second patient with,Bence,-Jones kappa,myeloma,is well,and skeletal pain and,Bence,-Jones,proteinuria,has disappeared 2 months after transplantation.,A third patient with,IgG,-lambda,myeloma,died of effusive,pericarditis,shortly after transplantation.,Acta,Med Scand 1986;219(5):523-7,Conclusion,Bone marrow transplantation may be indicated in a selective group of patients with multiple,myeloma,Acta,Med Scand 1986;219(5):523-7,Out of 690,allogenetic,matched sibling donor transplants for MM,344 were performed during the period 1983-93(all with BM)group 1,356 during 1994-98(223 with BM group 2 and 133 with PB group 3),the median age at transplantation of patients in group 1 was 43 years(range 21-62),In group 2,44 years(range 18_57)and in group 3,46 years(range 25_60),TBI+CY tended to be more commonly used in group 1(37%)and 2(39%)than in group 3(27%),Melphalan,containing regimes tended to be,morely,used in group 3,Melphalan,or,Busulphan,+CY rarely,Conditiong,regime,Engraftment,GVHD,Treatment related mortality,Treatment related mortality,Relapse rate,Relapse rate,Survival,Survival,Progression free survival,PFS was significantly better for group 2than for group 1(P,0.0001),With no significantly difference between group 2 and 3,Cause of death,75%in group 1,36%in group 2,33%in group 3,GVHD,Fungal,ARDS,Organ failure,Cause of death,the study shows that the improvement is entirely a result of a lower TRM during the latest 5-years period,aGVHD,has no changed during this,peroid,There was significant difference in deaths caused by IP and bacterial and,fungalinfection,Conditioning regime,TBI+Melphalan,has not,previrous,been,Shown to be superior to TBI+CY in this study,conclusion,Survival,3060%,Treatment related mortality,30%,Myeloablative,allogeneic,versus,autologous,transplantation,during the years 1983 to 1994,189,myeloma,patients who underwent,allo,-BMT with an HLA-identical sibling donor were compared retrospectively with an equal number of patients who received,a single,autologous,bone marrow or blood stem cell graft,And the ASCT patients were transplanted from 1986 to 1994,conclusion,The overall survival was significantly better for ASCT than for,allo,-BMT,with a median survival of 34 months and 18 months,respectively,(P,=.001),The main reason for the poorer survival in,allo,-BMT patients was higher TRM (41%,v,13%for ASCT,P,=.0001),which was not compensated for by a lower rate of relapse and progression,conclusion,However,in patients alive at 1 year,posttransplant,there was a trend for better long-term survival,(P,=.O9)and significantly better progression-free survival,(P,=.02)for,allo,-BMT as compared with ASCT,We conclude that the median survival is superior for ASCT,However,allo,-BMT has a lower relapse rate,which results in a similar long-term outcome for both approaches,but a longer follow-up is needed to assess the final outcome,Reduced-intensity conditioning,allogeneic,transplantation,The,Allo,-RIC was introduced in an attempt to decrease the transplant-related toxicity while retaining the beneficial,GvM,effect,1998 begin clinical study,19982003,We report the outcome of 229 patients,who received an allograft for,myeloma,with reduced-intensity conditioning(RIC),regimens from 33 centers within the EBMT.,With a median follow-up of 28 months,115 patients are,alive(range,1-53 months),The estimated overall survival at 3 years,is 40.6%(CI,33%-49%),The treatment-related mortalities at day 100,1,year,and2 years were 10%,22%,and 26%,respectively.,The cumulative probability of the progression-free survival was 21.3%(CI,15%-29%)at 3years,Conclusion,While RIC is feasible,heavily pretreated patients and patients with progressive disease do not benefit,RIC,vs,MAC,Data were available on a total of 516 patients from 103 centers:320 patients with RIC and 196 with MAC.,between January 1,1998,to December 31,2002,The median follow-up was 28 months,conclusion,RIC was associated with a reduction in TRM,but this was offset by an increase in relapse risk,the conditioning intensity did not impact on overall survival or retain significance for PFS,These data suggest that there is a continuing need to investigate dose intensity in the conditioning for,myeloma,allografts,.,Tandem,autologous/Allo,-RIC transplantation,Autologous,hematopoietic,cell,transplantation(HCT,)followed by,nonmyeloablative,allogeneicHCT(auto/,alloHCT,)provides,cytoreduction,and graft-versus-,myeloma,effects.,弗雷德哈钦森癌症研究中心,Patient inclusion criteria for this analysis were,stage II or III MM at diagnosis,available human leukocyte antigen(HLA)identical sibling donor,programmed sequential treatment with conventional,autologous,HCT followed by,nonmyeloablative,auto/,alloHCT,no prior,autologous,HCT.,105 patients with MM fulfilling those criteria were sequentially enrolled at 10 centers on 4 FHCRC-coordinated,multiinstitutional,protocols from August 1998 to August 2005,Patients proceeded to,allogeneic,HCT 40 to 180 days after,autografting,Autologous,HCT.,(G-CSF)mobilized peripheral blood mononuclear cells(G-PBMC)were harvested by,leukapheresis,after treatment with,cyclophosphamide,3 to 4 g/m2(day 1)and G-CSF 10 g/kg subcutaneously(from day 3 through collection),Autologous,HCT,38 patients received additional,paclitaxel,(250 mg/m2 per day,day 2),and 25 received additional,etoposide,(200 mg/m2 per day;days 1,2,3),and,dexamethasone,(10 mg/day orally;days 1,2,3,4),Two patients received G-CSF alone,.,Autologous,HCT,No treatment for MM was given between,autologous,and,allogeneic,HCT,Allogeneic,HCT,After recovery from,autologous,HCT,102,patientsproceeded,to,allotransplantation,.Donors were HLA-identical siblings,Nonmyeloablative,conditioning consisted in all patients of 2,Gy,total body irradiation(TBI)at 7,cGy,/min by linear accelerator or cobalt on day 0,27 patients received additional,fludarabine,(30 mg/m2)on days 4,3,and 2,N,%,Engraftment,All 102,allografted,patients had sustained engraftment.,On day 28,medians of 90%,95%,and 95%of peripheral blood T cells,granulocytes,and nucleated marrow,cells,respectively,were of donor origin.,This increased to medians of 96%to 100%on day 84,GVHD,43 patients(42%)developed grades 2 to 4 acute GVHD at a median of 42(range,8-107)days,74 patients(74%)developed chronic extensive GVHD at a median of 167(range,90-830)days after transplantation,.,NRM,NRM was 1%at day 100 and 11%,14%,and 18%at 1,2,and 5 years after,allografting,respectively,GVHD and infections were responsible for 18 of 19 non relapse related deaths.,Overall and progression-free survivals,After a median follow-up of 6.3 years after,allografting,(range 2-9),60 of 102(59%)patients survived and 33 of 102(32%)are in remission,Five-year estimated OS and PFS were 64%and 36%,respectively,conclusion,auto/,allo,-RIC HCT is a treatment option for patients with advanced stage MM,The addition of novel agents(,eg,thalidomide,bortezomib,and,lenalidomide,)as induction or,postgrafting,therapy,acting with GVM effects against disease-specific antigens,might further improve the outcome.,improve the outcome,Thalidomide/,lenalidomide,dexamethasone,Bortezomib,研究所佩奥利,-,Calmettes,，马赛，法国,This was a retrospective study from 3 centers,37 patients treated between November 2003 and March 2007,conclusion,bortezomib,is a safe and efficient option for,myeloma,patients after RIC-,allo,-SCT.,Double autologous,Versus,tandem auto/Allo-RIC transplantation,圣乔凡尼巴蒂斯塔大学医院，都灵，意大利,Methods,All patients were initially treated with VAD followed by,melphalan,and,autologous,stem-cell rescue,Patients with an HLA-identical sibling then received,nonmyeloablative,total-body irradiation and stem cells from the sibling.Patients,without an HLA-identical sibling received two consecutive,myeloablative,doses of,melphalan,each of which was followed by,autologous,stem-cell rescue.,The primary end points were overall survival and event-free survival.,Conclusions,Among patients with newly diagnosed,myeloma,survival in recipients of a,hematopoietic,stem-cell,autograft,followed by a stem-cell allograft from an HLA-identical sibling is superior to that in recipients of tandem stem-cell,autografts,.,UNSOLVED QUESTIONS IN ALLOGENEIC TRANSPLANTATION,Which is the best,allogeneic,transplantation approach?,Who are the patients most likely to benefit from,Allo,-RIC?,How to improve the results of,Allo,-RIC?,