High‐dose melphalan with autologous stem cell transplantation after VAD induction chemotherapy for treatment of amyloid light chain amyloidosis: a single centre prospective phase II study

Abstract

SummaryAmyloid light chain (AL) amyloidosis is the result of a clonal plasma cell expansion, in which monoclonal light chains transform to amyloid deposit in various tissues and can lead to organ dysfunction and organ failure. The median survival of patients with AL amyloidosis without therapy is 10–14 months. With high‐dose melphalan (HDM) and autologous stem cell transplantation (ASCT), haematological and clinical remission rates of up to 50% of treated patients have been reported from phase II studies. HDM followed by ASCT appears to prolong survival in patients, if haematological remission can be reached. In this phase II study, we evaluated vincristine, adriamycin and dexamethasone (VAD) as induction chemotherapy prior to stem cell mobilization and HDM with ASCT. The regimen was, in general, feasible in patients with AL amyloidosis, but VAD chemotherapy had a considerable World Health Organization (WHO) grade III–IV toxicity (25%) and mortality (7%) rate. VAD pretreatment did not interfere with stem cell mobilization and HDM with ASCT was possible in 86% of patients. The overall treatment efficacy was comparable with reported results of HDM and ASCT without preceding chemotherapy. We could not show an additional benefit of VAD induction in terms of increasing haematological response rate; however the 13% mortality rate after HDM and ASCT in our series was lower than the previous report.

Transplantation without growth factor: engraftment kinetics after stem cell transplantation for primary systemic amyloidosis (AL)

“…This practice is the custom in many of the European countries that perform stem cell transplantation. 20,21 Other investigators have also questioned whether postinfusion G-CSF administration has a clear financial benefit. 22 We demonstrated that in amyloidosis, it is also possible to perform stem cell transplantation as an outpatient procedure; however, the majority of patients who receive the transplant do require hospitalization (the median stay is 9 days).…”

Successful reduced intensity allogeneic stem cell transplantation for systemic AL amyloidosis

“…Numerous reports have described the availability of autologous PBSCT for systemic AL amyloidosis, but some reviews have reported high TRMs (13-39%) in autologous PBSCT for systemic AL amyloidosis [2][3][4][5][6][7]. Comenzo and Gertz [4] described TRM rates approaching 100% in patients with cardiac amyloidosis and clinical congestive heart failure or history of arrhythmia, syncope, or recurrent pleural effusion.…”

“…Less than 5% of all patients with systemic AL amyloidosis survive !10 years from the time of diagnosis. Several recent studies have reported the efficacy of autologous peripheral blood stem cell transplantation (PBSCT) for patients with systemic AL amyloidosis [2][3][4][5][6][7]. However, PBSCT can only be offered to a small proportion of patients, due to the high transplantrelated mortality (TRM), particularly in patients with cardiac amyloidosis.…”

High-dose therapy with auto-SCT is feasible in high-risk cardiac amyloidosis

“…[8][9][10] High-dose therapy with auto-SCT (HDT-ASCT) has been shown to be associated with long-term survival in AL patients. [11][12][13][14][15] However, high TRM ranging from 13 to 43%, especially in patients with cardiac involvement, questions the applicability of this treatment modality. 16 In order to answer this question, we performed a retrospective analysis of AL patients with cardiac involvement undergoing HDT-ASCT at our center.…”