1、Allogeneic haematopoietic cell transplantation for multiplemyelomanThe allogeneic transplant has the advantage over the autologous transplantnThe graft does not contain tumor cells and the potential for a graft versus myeloma (GvM) effectBone 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瑞典卡罗林斯卡医学院 1983Myeloablative conditioning n Three patients with multiple myeloma received bone marrow grafts from HLA-identical sibling donorsn One of the patients, with IgA kappa myeloma, refra
3、ctory to alkeran-prednisone therapy, is well and still without sign of disease 26 months post transplantationn A second patient with Bence-Jones kappa myeloma is well, and skeletal pain and Bence-Jones proteinuria has disappeared 2 months after transplantation.n A third patient with IgG-lambda myelo
4、ma died of effusive pericarditis shortly after transplantation. Acta Med Scand 1986;219(5):523-7Conclusion n Bone marrow transplantation may be indicated in a selective group of patients with multiple myelomaActa Med Scand 1986;219(5):523-7n Out of 690 allogenetic matched sibling donor transplants f
5、or MM n 344 were performed during the period 1983-93(all with BM ) group 1n 356 during 1994-98 (223 with BM group 2 and 133 with PB group 3)u the median age at transplantation of patients in group 1 was 43 years (range 21-62)uIn group 2 ,44 years (range 18_57) and in group 3, 46 years (range 25_60)u
6、 TBI+CY tended to be more commonly used in group 1(37%) and 2 (39%) than in group 3 (27%)uMelphalan containing regimes tended to be morely used in group 3 uMelphalan or Busulphan + CY rarely nConditiong regimeEngraftmentGVHD Treatment related mortalityTreatment related mortalityRelapse rate Relapse
7、rate SurvivalSurvivalnProgression free survivalu PFS was significantly better for group 2than for group 1(P0.0001)uWith no significantly difference between group 2 and 3nCause of death u 75% in group 1,36% in group 2 ,33 % in group 3 uGVHDuFungal uARDSuOrgan failurenCause of death u the study shows
8、that the improvement is entirely a result of a lower TRM during the latest 5-years periodu aGVHD has no changed during this peroid uThere was significant difference in deaths caused by IP and bacterial and fungalinfectionConditioning regime u TBI+Melphalan has not previrous been Shown to be superior
9、 to TBI+CY in this studynconclusion n Survival u 3060%nTreatment related mortalityu30%Myeloablative allogeneic versus autologous transplantationnduring the years 1983 to 1994n189 myeloma patients who underwent allo-BMT with an HLA-identical sibling donor were compared retrospectively with an equal n
10、umber of patients who received a single autologous bone marrow or blood stem cell graftnAnd the ASCT patients were transplanted from 1986 to 1994n conclusionn The overall survival was significantly better for ASCT than for allo-BMT, with a median survival of 34 months and 18 months, respectively (P
11、= .001), uThe 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 progressionn conclusionn However, in patients alive at 1 year posttransplant, there was a trend for better long-term sur
12、vival (P = .O9) and significantly better progression-free survival (P = .02) for allo-BMT as compared with ASCTn We conclude that the median survival is superior for ASCTn However, allo-BMT has a lower relapse rate, which results in a similar long-term outcome for both approaches, but a longer follo
13、w-up is needed to assess the final outcome Reduced-intensity conditioning allogeneic transplantationnThe Allo-RIC was introduced in an attempt to decrease the transplant-related toxicity while retaining the beneficial GvM effectn1998 begin clinical studyn 19982003nWe report the outcome of 229 patien
14、tswho received an allograft for myelomawith reduced-intensity conditioning (RIC)regimens from 33 centers within the EBMT.n With a median follow-up of 28 months, 115 patients are alive(range, 1-53 months)n The estimated overall survival at 3 years is 40.6% (CI, 33%-49%) n The treatment-related mortal
15、ities at day 100, 1 year,and 2 years were 10%, 22%, and 26%, respectively.n The cumulative probability of the progression-free survival was 21.3% (CI, 15%-29%) at 3yearsnConclusionnWhile RIC is feasible, heavily pretreated patients and patients with progressive disease do not benefit RIC vs MACnData
16、 were available on a total of 516 patients from 103 centers: 320 patients with RIC and 196 with MAC.nbetween January 1, 1998, to December 31, 2002nThe median follow-up was 28 monthsnconclusionn RIC was associated with a reduction in TRM but this was offset by an increase in relapse risk nthe conditi
17、oning intensity did not impact on overall survival or retain significance for PFSnThese data suggest that there is a continuing need to investigate dose intensity in the conditioning for myeloma allografts.Tandem autologous/Allo-RIC transplantationn Autologous hematopoietic cell transplantation(HCT)
18、 followed by nonmyeloablative allogeneic HCT (auto/alloHCT) provides cytoreduction and graft-versus-myeloma effects. 弗雷德哈钦森癌症研究中心弗雷德哈钦森癌症研究中心n Patient inclusion criteria for this analysis were ustage II or III MM at diagnosisu available human leukocyte antigen (HLA)identical sibling donoru programme
19、d sequential treatment with conventional autologous HCT followed by nonmyeloablative auto/alloHCT uno prior autologous HCT.n 105 patients with MM fulfilling those criteria were sequentially enrolled at 10 centers on 4 FHCRC-coordinated multiinstitutional protocols from August 1998 to August 2005n Pa
20、tients proceeded to allogeneic HCT 40 to 180 days after autograftingn Autologous HCT.u(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 collectio
21、n)n Autologous HCTu38 patients received additional paclitaxel (250 mg/m2 per day, day 2),uand 25 received additional etoposide (200 mg/m2 per day; days 1, 2, 3) uand dexamethasone (10 mg/day orally; days 1, 2,3, 4)uTwo patients received G-CSF alone.n Autologous HCTuNo treatment for MM was given betw
22、een autologous and allogeneic HCTn Allogeneic HCTu After recovery from autologous HCTu102 patientsproceeded to allotransplantation. Donors were HLA-identical siblingsn Nonmyeloablative conditioning consisted in all patients of 2 Gy total body irradiation (TBI) at 7 cGy/min by linear accelerator or c
23、obalt on day 0n 27 patients received additional fludarabine (30 mg/m2) on days 4, 3, and 2N%n EngraftmentnAll 102 allografted patients had sustained engraftment. nOn day 28, medians of 90%, 95%, and 95% of peripheral blood T cells, granulocytes, and nucleated marrow cells,respectively, were of donor
24、 origin.nThis increased to medians of 96% to 100% on day 84nGVHDu43 patients (42%) developed grades 2 to 4 acute GVHD at a median of 42 (range, 8-107) daysu74 patients (74%) developed chronic extensive GVHD at a median of 167 (range, 90-830) days after transplantation.n NRMnNRM was 1% at day 100 and
25、 11%, 14%, and 18% at 1, 2, and 5 years after allografting, respectivelynGVHD and infections were responsible for 18 of 19 non relapse related deaths.n Overall and progression-free survivalsuAfter a median follow-up of 6.3 years after allografting (range 2-9)u60 of 102 (59%)patients survived and 33
26、of 102 (32%) are in remissionuFive-year estimated OS and PFS were 64% and 36%,respectivelyn conclusionnauto/allo-RIC HCT is a treatment option for patients with advanced stage MMnThe addition of novel agents (eg,thalidomide, bortezomib, and lenalidomide) as induction or postgrafting therapy, acting
27、with GVM effects against disease-specific antigens, might further improve the outcome.n improve the outcomenThalidomide/lenalidomidendexamethasonenBortezomib研究所佩奥利研究所佩奥利- Calmettes，马赛，法国，马赛，法国 n This was a retrospective study from 3 centers 37 patients treated between November 2003 and March 2007n c
28、onclusionnbortezomib 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，意大利圣乔凡尼巴蒂斯塔大学医院，都灵，意大利 n Methodsn All patients were initially treated with VAD followed by melphalan and autologous stem-cell resc
29、uen Patients with an HLA-identical sibling then received nonmyeloablative total-body irradiation and stem cells from the sibling. Patientsn without an HLA-identical sibling received two consecutive myeloablative doses of melphalan, each of which was followed by autologous stem-cell rescue.n The prim
30、ary end points were overall survival and event-free survival.n ConclusionsnAmong 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.n UNSOLVED QUESTIONS IN ALLOGENEIC TRANSPLANTATIONuWhich is the best allogeneic transplantation approach?uWho are the patients most likely to benefit from Allo-RIC?uHow to improve the results of Allo-RIC?
