title: Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy.
abstract: Monoclonal immunoglobulin light chains are deposited as amyloid fibrils in systemic AL (primary) amyloidosis, but the underlying plasma cell dyscrasias are often difficult to detect or unquantifiable. The relationships between circulating monoclonal light chains, amyloid load and clinical outcome, and the relative efficacies of chemotherapy regimens aimed at suppressing monoclonal immunoglobulin production, have not been determined. Circulating free immunoglobulin light chain (FLC) concentration was measured with a sensitive nephelometric immunoassay in 262 patients with AL amyloidosis, and followed serially in 137 patients who received either high-dose chemotherapy or one of two intermediate-dose cytotoxic regimens. Amyloid load was quantified by serum amyloid P component scintigraphy. A monoclonal excess of FLC was identified at diagnosis in 98% of patients. Among 86 patients whose abnormal FLC concentration fell by more than 50% following chemotherapy, 5-year survival was 88% compared with only 39% among those whose FLC did not fall by half (P < 0.0001). Amyloid deposits regressed in 58 patients. The magnitude and duration of the FLC responses to intermediate- and high-dose chemotherapy regimens were similar. The FLC assay enabled the circulating fibril precursor protein in AL amyloidosis to be quantified and monitored in most patients. Reduction of the amyloidogenic FLC by more than 50% was associated with substantial survival benefit, regardless of the type of chemotherapy used. Clinical improvement following chemotherapy in AL amyloidosis is delayed, but treatment strategies can be guided by their early effect on serum FLC concentration.
authors.affiliation: The National Amyloidosis Centre and Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, London, UK.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Lachmann
authors.forename: Ruth
authors.initials: R
authors.lastname: Gallimore
authors.forename: Julian D
authors.initials: JD
authors.lastname: Gillmore
authors.forename: Hugh D
authors.initials: HD
authors.lastname: Carr-Smith
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Bradwell
authors.forename: Mark B
authors.initials: MB
authors.lastname: Pepys
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
mesh_terms: D000328:Adult; D000368:Aged; D000682:Amyloid / Q000032:analysis*; D000686:Amyloidosis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000911:Antibodies, Monoclonal / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry / Q000379:methods; D011877:Radionuclide Imaging; D000683:Serum Amyloid P-Component / Q000378:metabolism; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000682:Amyloid; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D000683:Serum Amyloid P-Component; C035222:amyloid protein AL