Effect of dose-intensive intravenous melphalan and autologous blood stem-cell transplantation on al amyloidosis-associated renal disease.
BACKGROUND
Dose-intensive intravenous melphalan with autologous blood stem-cell transplantation induces remission of the plasma cell dyscrasia in a substantial proportion of patients with AL amyloidosis. The impact of this treatment on associated renal disease is not known.


OBJECTIVE
To determine the effect of dose-intensive intravenous melphalan and autologous blood stem-cell transplantation on AL amyloidosis-associated renal disease.


METHODS
Prospective cohort study.


METHODS
Academic medical center.


METHODS
65 patients with AL amyloidosis and urinary protein excretion greater than 1 g/24 h who received dose-intensive intravenous melphalan and autologous blood stem-cell transplantation between 1 July 1994 and 30 June 1998.


METHODS
24-hour urinary protein excretion, serum cholesterol level, serum albumin level, creatinine clearance, urine and serum immunoelectrophoresis, and bone marrow biopsy. Renal response was defined as a greater than 50% reduction in urinary protein excretion in the absence of a 25% or greater reduction in creatinine clearance. Complete hematologic response was defined as absence of detectable monoclonal protein in serum and urine and a bone marrow specimen containing less than 5% plasma cells without clonal dominance of kappa or lambda isotype.


RESULTS
Among the 50 patients who survived for at least 12 months, proteinuria, hypoalbuminemia, and hypercholesterolemia improved during follow-up; 36% met criteria for a renal response. Median 24-hour urinary protein excretion decreased from a baseline value of 9.6 g/24 h to 1.6 g/24 h at 12 months among patients with complete hematologic response, and 71% met criteria for a renal response. Twenty-hour urinary protein excretion did not decrease during follow-up among patients with persistent plasma cell disease, and only 11% had a renal response at 12 months (P < 0.001 for hematologic responders vs. nonresponders).


CONCLUSIONS
Dose-intensive intravenous melphalan with autologous blood stem-cell transplantation improves the nephrotic syndrome in patients with AL amyloidosis-associated renal disease. The benefit is largely limited to patients achieving eradication of the underlying plasma cell dyscrasia.
Dember
L M
LM
Renal Section, EBRC 504, Boston University Medical Center, 650 Albany Street, Boston, MA 02118, USA. ldember@bu.edu
Sanchorawala
V
V
Seldin
D C
DC
Wright
D G
DG
LaValley
M
M
Berk
J L
JL
Falk
R H
RH
Skinner
M
M
D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000150:complications*; D002784:Cholesterol / Q000097:blood; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D007262:Infusions, Intravenous; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000150:complications* / Q000378:metabolism / Q000628:therapy*; D011507:Proteinuria / Q000517:prevention & control; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D002784:Cholesterol; D008558:Melphalan