Autologous stem cell transplantation (ASCT) is considered the gold standard in the frontline therapy of younger patients with multiple myeloma because it results in higher complete remission (CR) rates and longer event-free survival than conventional chemotherapy. The greatest benefit from ASCT is obtained in patients achieving CR after transplantation, the likelihood of CR being associated with the M-protein size at the time of transplantation. The incorporation of novel agents results in higher pre-and posttransplantation CR rates. Induction with bortezomibcontaining regimens is encouraging in patients with poor-risk cytogenetics. However, longer follow-up is required to assess the impact of this increased CR on long-term survival. The results of posttransplantation consolidation/maintenance with new drugs are encouraging. All this indicates that, in the era of novel agents, high-dose therapy should be optimized rather than replaced. Because of its high transplantation-related mortality, myeloablative allografting has been generally replaced by reduced-intensity conditioning (reduced intensity conditioning allogeneic transplantation). The best results are achieved after a debulky ASCT, with a progression-free survival plateau of 25% to 30% beyond 6 years from reduced intensity conditioning allogeneic transplantation. The development of novel reduced-intensity preparative regimens and peri-and posttransplantation strategies aimed at minimizing graft-versushost disease, and enhancing the graftversus-myeloma effect are key issues.
IntroductionThe outcome of patients with multiple myeloma (MM) treated with conventional chemotherapy is unsatisfactory. 1-3 A significant survival improvement has been observed for patients diagnosed in the more recent years. [4][5][6] Because the strongest survival increase was noted in patients younger than 60 years, the improvement was attributed, at least in part, to the benefit of high-dose therapy/stem cell transplantation (HDT/SCT). In addition, the long-term results of autologous and allogeneic transplantation show that a number of patients enjoy prolonged progression-free survival (PFS), and a small proportion of them can be cured. [7][8][9][10][11] Indeed, MM is the most frequent indication for HDT/SCT in Europe and the United States. 7,12 In recent years, the availability of new effective drugs, such as thalidomide, lenalidomide, and bortezomib, as well as the increased experience with the so-called dose-reduced intensity conditioning allogeneic transplantation (Allo-RIC), has resulted in a new scenario in which the role of HDT/SCT needs to be revisited. This review is focused on: (1) the impact of single and tandem autologous transplantation (ASCT) in the outcome of MM patients, (2) the results achieved with allogeneic transplantation (ie, myeloablative and Allo-RIC), and (3) the prospects for improvement with the incorporation of the new drugs in transplantation programs.
Autologous transplantation
Refractory and relapsed diseaseThe first studies on HDT/SCT in MM were per...
