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Dose-Intensive Melphalan With Blood Stem-Cell Support for the
Treatment of AL (Amyloid Light-Chain) Amyloidosis:
Survival and Responses in 25 Patients
Raymond L. Comenzo,
Evan Vosburgh,
Rodney H. Falk,
Vaishali Sanchorawala,
Johann Reisinger,
Simon Dubrey,
Laura M. Dember,
John L. Berk,
Gorgun Akpek,
Michael LaValley,
Carl O'Hara, Charles F. Arkin,
Daniel G. Wright, and
Martha Skinner
From the Amyloid Treatment and Research Program, Boston University
School of Medicine (BUSM); the Transfusion Medicine Program, Department
of Pathology and Laboratory Medicine and the Section of
Hematology-Oncology of the Department of Medicine; the Arthritis,
Cardiology, Renal, and Pulmonary Sections of the Department of
Medicine; and the Stem-cell Transplant Program, Boston Medical Center,
Boston, MA.
AL (amyloid light-chain) amyloidosis is an uncommon
plasma cell disorder in which depositions of amyloid light-chain
protein cause progressive organ failure and death in a median of 13 months. Autologous stem-cell transplantation is effective therapy for multiple myeloma and therefore, we evaluated its efficacy for AL
amyloidosis. Patients with adequate cardiac, pulmonary, and renal
function had stem cells mobilized with granulocyte-colony stimulating
factor and were treated with dose-intensive intravenous melphalan (200 mg/m2). Response to therapy was determined by survival and
improvement of performance status, complete response or persistence of
the clonal plasma cell disorder, and change in the function of organs involved with amyloid at baseline. We enrolled 25 patients with a
median age of 48 years (range, 29-60), all of whom had biopsy-proven amyloidosis with clonal plasma cell disorders. Twenty-two (88%) were
Southwest Oncology Group performance status 1 or 2 within a year of
diagnosis, and 16 (64%) had received no prior therapy. Predominant
amyloid-related organ involvement was cardiac (n = 8), renal (n = 7), hepatic (n = 6), neuropathic (n = 3), and lymphatic (n = 1).
Fifteen patients had one or two organ systems involved, whereas 10 had
three or more involved. With a median follow-up of 24 months (12-38),
17 of 25 patients (68%) are alive, and the median survival has not
been reached. Thirteen of 21 patients (62%) evaluated 3 months
posttransplant had complete responses of their clonal plasma cell
disorders. Currently, two thirds of the surviving patients (11 of 17)
have experienced improvements of amyloid-related organ involvement in
all systems, whereas 4 of 17 have stable disease. The improvement in
the median performance status of the 17 survivors at follow-up (0 [range, 0-3]) is statistically significant versus
baseline (2 [range, 1-3]; P < .01). Significant negative
prognostic factors with respect to overall survival include amyloid
involvement of more than two major organ systems and predominant cardiac involvement. Three patients have experienced relapses of the
clonal plasma cell disorder at 12 and 24 months. Dose-intensive therapy
should currently be considered as the preferred therapy for patients
with AL amyloidosis who meet functional criteria for autologous
transplantation.
Blood, Vol. 91 No. 10 (May 15), 1998:
pp. 3662-3670
© 1998 by The American Society of Hematology.
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