High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study

Ann Intern Med. 2004 Jan 20;140(2):85-93. doi: 10.7326/0003-4819-140-2-200401200-00008.


Background: 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.

Objective: 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.

Design: 8-year longitudinal analysis of clinical effectiveness.

Setting: University-affiliated specialty referral clinic.

Patients: 701 consecutive new patients with AL amyloidosis.

Intervention: High-dose chemotherapy and autologous stem-cell transplantation for patients who met eligibility requirements based on organ involvement and clinical status.

Measurements: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Amyloidosis / blood
  • Amyloidosis / complications
  • Amyloidosis / mortality
  • Amyloidosis / therapy*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Melphalan / administration & dosage*
  • Middle Aged
  • Stem Cell Transplantation*
  • Survival Analysis
  • Transplantation, Autologous


  • Melphalan