Effect of dose-intensive intravenous melphalan and autologous blood stem-cell transplantation on al amyloidosis-associated renal disease.

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 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).

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.

• Authors: L M Dember, V Sanchorawala, D C Seldin, D G Wright, M LaValley, J L Berk, R H Falk, M Skinner
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 134 Issue 9 Pt 1 Pg. 746-53 (May 01 2001) ISSN: 0003-4819 [Print] United States
• PMID: 11329232 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cholesterol
• Melphalan

Topics

• Adult
• Aged
• Amyloidosis (complications)
• Cholesterol (blood)
• Combined Modality Therapy
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Hypercholesterolemia (metabolism)
• Infusions, Intravenous
• Male
• Melphalan (administration & dosage, adverse effects)
• Middle Aged
• Nephrotic Syndrome (complications, metabolism, therapy)
• Proteinuria (prevention & control)
• Transplantation, Autologous
• Treatment Outcome