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


METHODS
8-year longitudinal analysis of clinical effectiveness.


METHODS
University-affiliated specialty referral clinic.


METHODS
701 consecutive new patients with AL amyloidosis.


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


METHODS
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.
Skinner
Martha
M
Boston University School of Medicine, Boston, Massachusetts 02118, USA. mskinner@bu.edu
Sanchorawala
Vaishali
V
Seldin
David C
DC
Dember
Laura M
LM
Falk
Rodney H
RH
Berk
John L
JL
Anderson
Jennifer J
JJ
O'Hara
Carl
C
Finn
Kathleen T
KT
Libbey
Caryn A
CA
Wiesman
Janice
J
Quillen
Karen
K
Swan
Niall
N
Wright
Daniel G
DG
D000368:Aged; D000686:Amyloidosis / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D014182:Transplantation, Autologous
D008558:Melphalan