High-Dose Melphalan and Autologous Stem-Cell Transplantation in Patients with AL Amyloidosis: An 8-Year Study

TLDR

AL amyloidosis is a fatal disease caused by deposition of monoclonal immunoglobulin light‑chain amyloid fibrils in tissues. The study evaluated 8‑year survival and organ response in a large cohort of AL amyloidosis patients treated with high‑dose intravenous melphalan and autologous stem‑cell transplantation. Eligible patients received high‑dose melphalan (100–200 mg/m²) followed by autologous stem‑cell transplantation, and outcomes were assessed by survival analysis of the entire cohort and a detailed subgroup analysis. Among 312 treated patients, median survival was 4.6 years, 40 % achieved complete hematologic response associated with longer survival, end‑organ disease improved—especially in responders—while 100‑day mortality was 13 % (higher in cardiomyopathy), and the regimen yielded hematologic remission, improved 5‑year survival, and reversal of amyloid‑related organ damage in many.

Abstract

AL amyloidosis is a fatal disease resulting from tissue deposition of amyloid fibrils derived from monoclonal immunoglobulin light chains. Treatment with oral chemotherapy is minimally effective.To test survival and organ response in a large sample of patients treated with high-dose intravenous melphalan (100 to 200 mg/m2) and autologous blood stem-cell transplantation.8-year longitudinal analysis of clinical effectiveness.University-affiliated specialty referral clinic.701 consecutive new patients with AL amyloidosis.High-dose chemotherapy and autologous stem-cell transplantation for patients who met eligibility requirements based on organ involvement and clinical status.Survival analysis of all patients evaluated and a detailed analysis of treatment outcome in the subgroup that received high-dose melphalan and stem-cell transplantation.Among 701 patients with AL amyloidosis, 394 (56%) were eligible for high-dose melphalan and stem-cell transplantation; 82 did not proceed with treatment because of patient choice or disease progression. Median survival of the 312 patients who initiated treatment was 4.6 years. A complete hematologic response, defined as no evidence of an underlying plasma cell dyscrasia 1 year after treatment, was achieved in 40% of patients and was associated with prolonged survival. Statistically significant improvements occurred in end-organ disease and were greater in patients with a complete hematologic response. Mortality rate within 100 days of treatment with high-dose melphalan and stem-cell transplantation was 13%; patients with cardiomyopathy had the highest mortality rates.Treatment of selected patients with AL amyloidosis by using high-dose melphalan and stem-cell transplantation resulted in hematologic remission, improved 5-year survival, and reversal of amyloid-related disease in a substantial proportion.