[临床医学]异基因造血干细胞移植治疗多发性骨髓瘤.ppt

Allogeneic haematopoietic cell transplantation for multiple myeloma,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 myelomaGahrton G, Ringdén O, Lönnqvist 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 alkeran-prednisone therapy, is well and still without sign of disease 26 months post transplantationA 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 periodaGVHD 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 30~60% Treatment –related mortality 30%,,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 receiveda single autologous bone marrow or blood stem cell graftAnd 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,,conclusionHowever, 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 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-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,1998~2003We 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 yearsis 40.6% (CI, 33%-49%) The treatment-related mortalities at day 100, 1 year,and 2 years were 10%, 22%, and 26%, 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: 320 patients with RIC and 196 with MAC.between January 1, 1998, to December 31, 2002The median follow-up was 28 months,,,,,,,,,,,,,,,,,,,,,,,,,,,,,conclusionRIC 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.,。