Article    Table of Contents                    Full Text of this article    PDF of this article (PDFs free after 6 months)    Summary for Patients    Summary for Patients (PDF)    Figures/Tables List    Related articles in Annals  Services    Send comment/rapid response letter    Notify a friend about this article    Alert me when this article is cited    Add to Personal Archive    Download to Citation Manager    ACP Search                            Get Permissions  Google Scholar    Search for Related Content  PubMed Articles in PubMed by Author:    Dember, L. M.    Skinner, M.    Related Articles in PubMed    PubMed Citation    PubMed

ARTICLE

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

Laura M. Dember, MD; Vaishali Sanchorawala, MD; David C. Seldin, MD, PhD; Daniel G. Wright, MD; Michael LaValley, PhD; John L. Berk, MD; Rodney H. Falk, MD; and Martha Skinner, MD

1 May 2001 | Volume 134 Issue 9 Part 1 | Pages 746-753

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 or 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.

Author and Article Information

From Boston University School of Medicine, Boston, Massachusetts.

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.

Related articles in Annals:

Summaries for Patients
Melphalan plus Stem-Cell Transplantation Improves Kidney Function in Patients with Primary Amyloidosis

Annals 2001 134: S91. [Full Text]  

This article has been cited by other articles:

				D. J. Salant, V. Sanchorawala, and V. D. D'Agati A Case of Atypical Light Chain Deposition Disease--Diagnosis and Treatment Clin. J. Am. Soc. Nephrol., July 1, 2007; 2(4): 858 - 867. [Full Text] [PDF]

				L. M. Dember, P. N. Hawkins, B. P.C. Hazenberg, P. D. Gorevic, G. Merlini, I. Butrimiene, A. Livneh, O. Lesnyak, X. Puechal, H. J. Lachmann, et al. Eprodisate for the Treatment of Renal Disease in AA Amyloidosis N. Engl. J. Med., June 7, 2007; 356(23): 2349 - 2360. [Abstract] [Full Text] [PDF]

				N. Leung, A. Dispenzieri, M. Q. Lacy, S. K. Kumar, S. R. Hayman, F. C. Fervenza, S. S. Cha, and M. A. Gertz Severity of Baseline Proteinuria Predicts Renal Response in Immunoglobulin Light Chain-Associated Amyloidosis after Autologous Stem Cell Transplantation Clin. J. Am. Soc. Nephrol., May 1, 2007; 2(3): 440 - 444. [Abstract] [Full Text] [PDF]

				L. M. Dember Amyloidosis-Associated Kidney Disease J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3458 - 3471. [Abstract] [Full Text] [PDF]

				D. C. Seldin, J. J. Anderson, M. Skinner, K. Malek, D. G. Wright, K. Quillen, K. Finn, B. Oran, and V. Sanchorawala Successful treatment of AL amyloidosis with high-dose melphalan and autologous stem cell transplantation in patients over age 65 Blood, December 1, 2006; 108(12): 3945 - 3947. [Abstract] [Full Text] [PDF]

				V. Sanchorawala Light-Chain (AL) Amyloidosis: Diagnosis and Treatment Clin. J. Am. Soc. Nephrol., November 1, 2006; 1(6): 1331 - 1341. [Abstract] [Full Text] [PDF]

				S. M. Korbet and M. M. Schwartz Multiple Myeloma J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2533 - 2545. [Full Text] [PDF]

				M. Haubitz and D. Peest Myeloma - new approaches to combined nephrological-haematological management Nephrol. Dial. Transplant., March 1, 2006; 21(3): 582 - 590. [Full Text] [PDF]

				L. M. Dember, J.-A. O. Shepard, F. Nesta, and J. R. Stone Case 15-2005 - An 80-Year-Old Man with Shortness of Breath, Edema, and Proteinuria N. Engl. J. Med., May 19, 2005; 352(20): 2111 - 2119. [Full Text] [PDF]

				A. Dispenzieri, M. A. Gertz, R. A. Kyle, M. Q. Lacy, M. F. Burritt, T. M. Therneau, J. P. McConnell, M. R. Litzow, D. A. Gastineau, A. Tefferi, et al. Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation Blood, September 15, 2004; 104(6): 1881 - 1887. [Abstract] [Full Text] [PDF]

				D. C. Seldin, J. J. Anderson, V. Sanchorawala, K. Malek, D. G. Wright, K. Quillen, K. T. Finn, J. L. Berk, L. M. Dember, R. H. Falk, et al. Improvement in quality of life of patients with AL amyloidosis treated with high-dose melphalan and autologous stem cell transplantation Blood, September 15, 2004; 104(6): 1888 - 1893. [Abstract] [Full Text] [PDF]

				M. Skinner, V. Sanchorawala, D. C. Seldin, L. M. Dember, R. H. Falk, J. L. Berk, J. J. Anderson, C. O'Hara, K. T. Finn, C. A. Libbey, et al. High-Dose Melphalan and Autologous Stem-Cell Transplantation in Patients with AL Amyloidosis: An 8-Year Study Ann Intern Med, January 20, 2004; 140(2): 85 - 93. [Abstract] [Full Text] [PDF]

				M. Zeier, J. Perz, R. P. Linke, U. Donini, R. Waldherr, K. Andrassy, A. D. Ho, and H. Goldschmidt No regression of renal AL amyloid in monoclonal gammopathy after successful autologous blood stem cell transplantation and significant clinical improvement Nephrol. Dial. Transplant., December 1, 2003; 18(12): 2644 - 2647. [Abstract] [Full Text] [PDF]

				R. Snanoudj, M.-F. Mamzer-Bruneel, O. Hermine, J.-P. Grunfeld, and D. Chauveau Recovery of acute renal failure and nephrotic syndrome following autologous stem cell transplantation for primary (AL) amyloidosis Nephrol. Dial. Transplant., October 1, 2003; 18(10): 2175 - 2177. [Full Text] [PDF]

				G. Merlini and V. Bellotti Molecular Mechanisms of Amyloidosis N. Engl. J. Med., August 7, 2003; 349(6): 583 - 596. [Full Text] [PDF]