High-dose melphalan and peripheral blood stem cell transplantation for light-chain amyloidosis with cardiac involvement

Abstract

High-dose melphalan (HDM) plus stem cell transplantation is an effective treatment for light-chain amyloidosis (AL), but is associated with high treatment-related mortality in patients with cardiac involvement. We studied 187 patients with cardiac involvement with AL who underwent HDM between 1996 and 2008. The median age was 57 years and the median time from diagnosis to HDM was 3.6 months. Half of the patients received reduceddose melphalan (100-160 mg/m 2 ). The median overall survival (OS) was 66 months, 54 months from diagnosis and HDM, respectively, and 91 patients (49%) were alive at the last follow-up 52 months (median) from HDM. Thirty patients (16%) died within 100 days of transplantation; only low serum albumin predicted early deaths. Overall, hematologic response (HR) and cardiac responses were seen in 66% and 41% of patients, respectively. The median OS for patients with and without HR was not reached and 22 months, respectively (P < .01); and for those with any decrease and no decrease in N-terminal-pro-brain natriuretic peptide was not reached and 26 months, respectively (P < .01). In multivariate analysis of baseline factors, only reduceddose melphalan predicted shorter OS. HDM is feasible in patients with cardiac amyloidosis, and achievement of HR and organ response is associated with improved survival. (Blood. 2012;119(5): 1117-1122) IntroductionAmyloidosis is a group of rare diseases characterized by multiorgan deposition of amyloid fibrils. In light-chain (AL) amyloidosis or primary systemic amyloidosis, the fibrils are derived from the immunoglobulin light chains secreted by clonal plasma cells. 1 AL amyloidosis represents the most common type of systemic amyloidosis and cardiac involvement is seen in more than half of patients at diagnosis. It affects approximately 10 patients per million per year, including 10%-15% of patients with multiple myeloma (MM). 2,3 The treatment approaches used for AL amyloidosis are directed toward the eradication of the abnormal plasma cell clone with the aim of eliminating the supply of the amyloidogenic light chains. 4 Compared with myeloma, AL is typically associated with a lower burden of clonal plasma cells. 5 High-dose melphalan (HDM) and peripheral blood stem cell transplantation (SCT) have been used since the mid-1990s and remain an effective treatment for AL amyloidosis. 6-8 However, the transplantation-related mortality (TRM) in AL amyloidosis (approximately 10%-15%) is significantly higher than that seen in patients with MM and lymphoma (1%-2%) and is often attributed to the presence of underlying cardiac and/or multiorgan involvement. 9 The outcome with HDM among patients with cardiac amyloidosis has not been examined systematically. Therefore, we undertook the present study to examine the outcome of patients with AL amyloidosis receiving HDM, with particular focus on transplantation-related complications, hematologic response (HR) and organ response rates, impact on cardiac function, and factors predicting post-HDM survival. MethodsWe selected the ...

Safety and efficacy of high-dose melphalan and auto-SCT in patients with AL amyloidosis and cardiac involvement

“…TRM following HDM/SCT in this current report was 4%, and was 8% for modified cardiac biomarker stage III disease (P ¼ 0.623). It did not correlate with serum albumin of o2.5 g/dL, which has been demonstrated by Madan et al 7 We attribute this low TRM to patient selection, optimal pre-and post-transplant supportive care, and the experience of multi-disciplinary team members. Patient selection was dependent upon an objective assessment of functional status, such as exercise oximetry, stair climbing and formal CPET.…”

“…In HDM/SCT, hematologic CR correlates with EFS, OS, cardiac response and reduction in cardiac biomarkers. 7,13 Patients who do not achieve a VGPR or have a less than 90% reduction in serum FLCs exhibit a much worse prognosis. 16,17 In our series, the hematologic CR rate was 27% by intention-to-treat analysis, which compares with 43% in all evaluable patients with AL amyloidosis treated with HDM/SCT in our previous series.…”

“…TnI correlated with treatment-related mortality (TRM). 3 Recently, Madan et al 7 expanded their analysis to include patients with cardiac involvement that were treated with HDM/SCT. In this retrospective analysis, cardiac biomarker staging was not predictive for OS, but did correlate with a reduced dose of melphalan, which was an independent variable for shorter survival.…”

PBSC mobilization in newly diagnosed patients with POEMS syndrome: outcomes and prognostic factors

“…It is reported that reduced dose of melphalan is only one prognostic factor for shorter OS in patients with light-chain amyloidsis who receive autologous transplantation. 19 Thus, the long-term followup is needed to evaluate this effect.…”

Nuclear imaging of cardiac amyloidosis

“…Patients with AL-CA may see improvement in their survival of up to 12 years with appropriate chemotherapy. 5,6 The traditional treatment for TTR-CA is liver transplantation, with novel pharmacological agents under development. 7 In the face of these advances and prognostic implications of CA, it is essential to make the correct diagnosis using prompt and reliable non-invasive imaging modalities.…”