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 s ubstantial proportion of patients with AL amyloidosis. The impact of this t reatment 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 gre ater than 1 g/24 h who received dose-intensive intravenous melphalan and au tologous blood stem-cell transplantation between 1 July 1994 and 30 June 19 98, Measurements: 24-hour urinary protein excretion, serum cholesterol level, s erum albumin level, creatinine clearance, urine and serum immunoelectrophor esis, 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 great er reduction in creatinine clearance. Complete hematologic response was def ined as absence of detectable monoclonal protein in serum and urine and a b one marrow specimen containing less than 5% plasma cells without clonal dom inance of kappa or lambda isotype. Results: Among the 50 patients who survived for at least 12 months, protein uria, hypoalbuminemia, and hypercholesterolemia improved during follow-up; 36% met criteria for a renal response. Median 24-hour urinary protein excre tion decreased from a baseline value of 9.6 g/24 h to 1.6 g/24 h at 12 mont hs among patients with complete hematologic response, and 71% met criteria for a renal response. Twenty-hour urinary protein excretion did not decreas e 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 respo nders vs, nonresponders). Conclusion: Dose-intensive intravenous melphalan with autologous blood stem -cell transplantation improves the nephrotic syndrome In patients with AL a myloidosis-associated renal disease. The benefit is largely limited to pati ents achieving eradication of the underlying plasma cell dyscrasia.