Effect of Dose-Intensive Intravenous Melphalan and Autologous Blood Stem-Cell Transplantation on AL Amyloidosis–Associated Renal Disease

Effect of Dose-Intensive Intravenous Melphalan and Autologous Blood Stem-Cell Transplantation on AL Amyloidosis–Associated Renal Disease

From Boston University School of Medicine, Boston, Massachusetts.

Abstract

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.

Design: Prospective cohort study.

Setting: Academic medical center.

Patients: 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.

Measurements: 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 κ or λ 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).

Conclusion: 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.

Article and Author Information

Acknowledgments: The authors thank Raymond Comenzo, MD, for helpful review of the manuscript and Kathleen Finn, RN, Karen Donovan, and Akira Murakami for assistance with data collection.
Grant Support: By the U.S. Food and Drug Administration (Fd-R-001346), the Young Family Amyloid Research Fund, the Sue Sellors Finley Cardiac Amyloid Research Fund, and the Amyloid Research Fund.
Requests for Single Reprints: Laura M. Dember, MD, Renal Section, EBRC 504, Boston University Medical Center, 650 Albany Street, Boston, MA 02118; e-mail, ldember{at}bu.edu.
Current Author Addresses: Dr. Dember: Renal Section, EBRC 504, Boston University Medical Center, 650 Albany Street, Boston, MA 02118.
Dr. Sanchorawala: Hematology Oncology, F3, Boston University Medical Center, 88 East Newton Street, Boston, MA 02118.
Drs. Seldin and Wright: Hematology–Oncology Section, EBRC 4, Boston University Medical Center, 650 Albany Street, Boston, MA 02118.
Dr. LaValley: Arthritis Center, A203, Boston University Medical Center, 88 East Newton Street, Boston, MA 02118.
Dr. Berk: Pulmonary Section, R3, Boston University Medical Center, 88 East Newton Street, Boston, MA 02118.
Dr. Falk: Cardiology Section, D822, Boston University Medical Center, 88 East Newton Street, Boston, MA 02118.
Dr. Skinner: Amyloid Program, EB33, Boston University Medical Center, 15 Albany Street, Boston, MA 02118.
Author Contributions: Conception and design: L.M. Dember, V. Sanchorawala, D.C. Seldin, D.G. Wright, R.H. Falk, M. Skinner.
Analysis and interpretation of the data: L.M. Dember, M. LaValley.
Drafting of the article: L.M. Dember, J.L. Berk.
Critical revision of the article for important intellectual content: V. Sanchorawala, D.C. Seldin, D.G. Wright, M. LaValley, J.L. Berk, R.H. Falk, M. Skinner.
Final approval of the article: L.M. Dember, V. Sanchorawala, D.C. Seldin, D.G. Wright, M. LaValley, J.L. Berk, R.H. Falk, M. Skinner.
Provision of study materials or patients: L.M. Dember, V. Sanchorawala, D.C. Seldin, D.G. Wright, R.H. Falk, M. Skinner.
Statistical expertise: M. LaValley.
Obtaining of funding: M. Skinner.
Administrative, technical, or logistic support: D.G. Wright, M. Skinner.
Collection and assembly of data: L.M. Dember, V. Sanchorawala, M. Skinner.