Hematopoietic stem cell transplantation for multiple myeloma beyond 2010

Abstract

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...

Allogeneic hematopoietic SCT in multiple myeloma: long-term results from a single institution

“…4,5,9,15,17 Although allo-HCT with conventional MAC is associated with a high TRM, it is of interest that 10-25% of patients undergoing an allogeneic transplant are long-term disease free and likely cured. 4,5,9,15 Garhton et al 6 reported the EBMT experience showing a significant decrease in TRM over time (from 46% in the period 1983-1993 to 30% between 1994 and 1998). Unfortunately, in a more recent EBMT study, the TRM with allo-MAC for the period 1998-2002 was 37%.…”

“…Despite a reported PFS of 25% beyond 7 years, 8 the role of allo-RIC remains controversial. 9 However, it must be considered that allo-RIC is often done in advanced stages of the disease, when the chances of success are particularly low, as most patients with high-risk myeloma (that is, those with early relapse or high-risk cytogenetics and advanced international staging system (ISS) score) 10,11 still have a dismal prognosis even when treated with novel agents.…”

Bortezomib, Dexamethasone, and High-Dose Melphalan as Conditioning for Stem Cell Transplantation in Young Japanese Multiple Myeloma Patients: A Pilot Study

“…It seems that achieving CR is crucial for a long-lasting response and prolonged survival [7]. Patients who achieve immunofixation-negative CR after ASCT have significantly longer event-free survival and overall survival than those who remain in partial remission (PR) [5]. Thus, several approaches have been tried to enhance the response to transplantation, but there have been problems with higher morbidity and mortality compared to HDM, which remains the recommended regimen [24][25][26].…”

“…Conventional chemotherapy rarely achieves a major response, so high-dose chemotherapy with autologous stem cell transplantation (ASCT) is the standard treatment for MM patients under 65 years old [3,4]. After ASCT, a number of patients achieve prolonged progression-free survival [3][4][5][6][7][8]. Among several conditioning regimens, high-dose melphalan (HDM; 200 mg/m 2 ) is the recommended standard regimen for use before ASCT, because of its efficiency and acceptable toxicity [9].…”

Cranial Plasmacytoma: A Case Series and Review of the Literature

“…This subject has been reviewed extensively in the literature, with a number of potent novel agents available [20][21][22][23]. In addition, the plasmacytoma may be managed with additional radiotherapy typically given for pain relief if systemic therapy could not control it, or when neurological fall-out or impingement on vital structures occurs, as was done in the second case.…”