《异基因造血干细胞移植治疗多发性骨髓瘤》由会员分享，可在线阅读，更多相关《异基因造血干细胞移植治疗多发性骨髓瘤（93页珍藏版）》请在金锄头文库上搜索。
1、异基因造血干细胞移植治疗多发性骨髓瘤Stillwatersrundeep.流静水深流静水深,人静心深人静心深Wherethereislife,thereishope。有生命必有希望。有生命必有希望nThe 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
2、 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瑞典卡罗林斯卡医学院 1983Myeloablative conditioning nThree patients with multiple myeloma received bone marrow grafts from HLA-identical sibling donorsnOne of the patients,
3、 with IgA kappa myeloma, refractory 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.nA third
4、patient with IgG-lambda myeloma 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 matche
5、d sibling donor transplants for MM n344 were performed during the period 1983-93(all with BM ) group 1n356 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
6、 3, 46 years (range 25_60)u 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 mor
7、talityRelapse rate Relapse 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
8、of death u the study shows 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 previrou
9、s been Shown to be superior 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 retr
10、ospectively with an equal number of patients who received a single autologous bone marrow or blood stem cell graftnAnd the ASCT patients were transplanted from 1986 to 1994nconclusionnThe overall survival was significantly better for ASCT than for allo-BMT, with a median survival of 34 months and 18
11、 months, respectively (P = .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 conclusionnHowever, in patients alive at 1 year posttransplant, there was a trend
12、for better long-term survival (P = .O9) and significantly better progression-free survival (P = .02) for allo-BMT as compared with ASCTnWe conclude that the median survival is superior for ASCTnHowever, allo-BMT has a lower relapse rate, which results in a similar long-term outcome for both approach
13、es, but a longer follow-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
14、 outcome of 229 patientswho received an allograft for myelomawith reduced-intensity conditioning (RIC)regimens from 33 centers within the EBMT.nWith a median follow-up of 28 months, 115 patients are alive(range, 1-53 months)nThe estimated overall survival at 3 years is 40.6% (CI, 33%-49%) nThe treat
15、ment-related mortalities at day 100, 1 year,and 2 years were 10%, 22%, and 26%, respectively.nThe 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 benef
16、it RIC vs MACnData 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
17、 risk nthe conditioning 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 tr
18、ansplantation(HCT) 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 siblin
19、g donoru programmed 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
20、to August 2005n Patients 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
21、 through collection)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
22、 MM was given between 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 linea
23、r accelerator or cobalt on day 0n27 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,respective
24、ly, were of donor 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
25、1% at day 100 and 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
26、 survived and 33 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
27、 therapy, acting 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
28、and March 2007n conclusionnbortezomib 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 autologo
29、us stem-cell rescuenPatients with an HLA-identical sibling then received nonmyeloablative total-body irradiation and stem cells from the sibling. Patientsnwithout an HLA-identical sibling received two consecutive myeloablative doses of melphalan, each of which was followed by autologous stem-cell re
30、scue.nThe primary 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?
