High-dose intravenous melphalan and autologous stem cell transplantation as initial therapy or following two cycles of oral chemotherapy for the treatment of AL amyloidosis: results of a prospective randomized trial.
A prospective randomized trial was conducted to study the timing of high-dose intravenous melphalan and autologous stem cell transplantation (HDM/SCT) in AL amyloidosis. In all, 100 newly diagnosed patients were randomized to receive HDM/SCT, either as initial therapy (Arm-1) or following two cycles of oral melphalan and prednisone (Arm-2). The objectives of the trial were to compare survival and hematologic and clinical responses. With a median follow-up of 45 months (range 24-70), the overall survival was not significantly different between the two treatment arms (P=0.39). The hematologic response and organ system improvements after treatment did not differ between the two groups. Fewer patients received HDM/SCT in Arm-2 because of disease progression during the oral chemotherapy phase of the study, rendering them ineligible for subsequent high-dose therapy. This affected patients with cardiac involvement particularly, and led to a trend for an early survival disadvantage in Arm-2. Hence, newly diagnosed patients with AL amyloidosis eligible for HDM/SCT did not benefit from initial treatment with oral melphalan and prednisone, and there was a survival disadvantage for patients with cardiac involvement if HDM/SCT was delayed by initial oral chemotherapy.
Sanchorawala
V
V
Hematology and Stem Cell Transplant Programs, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USA. Vaishali.Sanchorawala@bmc.org
Wright
D G
DG
Seldin
D C
DC
Falk
R H
RH
Finn
K T
KT
Dember
L M
LM
Berk
J L
JL
Quillen
K
K
Anderson
J J
JJ
Comenzo
R L
RL
Skinner
M
M
D000686:Amyloidosis / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006331:Heart Diseases / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007674:Kidney Diseases / Q000628:therapy; D007937:Leukapheresis; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000633:toxicity; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan; D011241:Prednisone