1、Allogeneic haematopoietic cell transplantation for multiplemyeloma,The allogeneic transplant has the advantage over the autologous transplantThe graft does not contain tumor cells and the potential for a graft versus myeloma (GvM) effect,Bone marrow transplantation in three patients with multiple my
2、eloma 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 donorsOne of the patients, with IgA kappa myeloma, refractory to al
3、keran-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 eff
4、usive 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
5、performed during the period 1983-93(all with BM ) group 1356 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 m
6、ore 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,Surviva
7、l,Progression free survival,PFS was significantly better for group 2than for group 1(P0.0001)With no significantly difference between group 2 and 3,Cause of death,75% in group 1,36% in group 2 ,33 % in group 3 GVHDFungal ARDSOrgan failure,Cause of death,the study shows that the improvement is entire
8、ly 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,conclusi
9、on,Survival 3060%Treatment related mortality30%,Myeloablative allogeneic versus autologous transplantation,during the years 1983 to 1994189 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
10、 autologous bone marrow or blood stem cell graftAnd the ASCT patients were transplanted from 1986 to 1994,conclusionThe 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 sur
11、vival 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,conclusionHowever, in patients alive at 1 year posttransplant, there was a trend for better long-term survival (P = .O9) and significantly better progre
12、ssion-free survival (P = .02) for allo-BMT as compared with ASCTWe conclude that the median survival is superior for ASCTHowever, 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-
13、intensity conditioning allogeneic transplantation,The Allo-RIC was introduced in an attempt to decrease the transplant-related toxicity while retaining the beneficial GvM effect1998 begin clinical study,19982003We report the outcome of 229 patientswho received an allograft for myelomawith reduced-in
14、tensity 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,and 2 years were 10%, 22%, and 26%
15、, respectively.The cumulative probability of the progression-free survival was 21.3% (CI, 15%-29%) at 3years,ConclusionWhile 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: 3
16、20 patients with RIC and 196 with MAC.between January 1, 1998, to December 31, 2002The 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 signi
17、ficance for PFSThese 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 allogeneic HCT (auto/alloHCT) provide
18、s 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 nonmyeloablativ
19、e 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
20、-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 HCT38 patients received additional paclitaxel (250 mg/m2 per day, day 2),a
21、nd 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 HCTNo treatment for MM was given between autologous and allogeneic HCT,Allogeneic HCT After recovery from autologous HCT102 patients
22、proceeded 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 027 patients received additional fludarabine (30 mg/m2) on days 4, 3, and 2,N,%,Engraf
23、tmentAll 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,GVHD43 patients (42%) developed grades 2 to
24、 4 acute GVHD at a median of 42 (range, 8-107) days74 patients (74%) developed chronic extensive GVHD at a median of 167 (range, 90-830) days after transplantation.,NRMNRM was 1% at day 100 and 11%, 14%, and 18% at 1, 2, and 5 years after allografting, respectivelyGVHD and infections were responsibl
25、e for 18 of 19 non relapse related deaths.,Overall and progression-free survivalsAfter 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 remissionFive-year estimated OS and PFS were 64% and 36%,respectively,conclusionauto/allo-R
26、IC HCT is a treatment option for patients with advanced stage MMThe 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 outcomeThalidomi
27、de/lenalidomidedexamethasoneBortezomib,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,conclusionbortezomib is a safe and efficient option for myeloma patients after RIC-allo-SCT.,Double autologous Versus tandem auto/Allo
28、-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. Patientswithout an HLA-ide
29、ntical 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.,ConclusionsAmong patients with newly diagnosed myeloma, survival in recipients of a hematopoietic
30、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 TRANSPLANTATIONWhich 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?,
