title: Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements.
abstract: OBJECTIVE
  Cardiac involvement predicts poor prognosis in light chain (AL) amyloidosis, and the current prognostic classification is based on cardiac biomarkers troponin-T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-ProBNP). However, long-term outcome is dependent on the underlying plasma cell clone, and incorporation of clonal characteristics may allow for better risk stratification.
  
  
  METHODS
  We developed a prognostic model based on 810 patients with newly diagnosed AL amyloidosis, which was further examined in two other datasets: 303 patients undergoing stem-cell transplantation, and 103 patients enrolled onto different clinical trials.
  
  
  RESULTS
  We examined the prognostic value of plasma cell-related characteristics (ie, difference between involved and uninvolved light chain [FLC-diff], marrow plasma cell percentage, circulating plasma cells, plasma cell labeling index, and β(2) microglobulin). In a multivariate model that included these characteristics as well as cTnT and NT-ProBNP, only FLC-diff, cTnT, and NT-ProBNP were independently prognostic for overall survival (OS). Patients were assigned a score of 1 for each of FLC-diff ≥ 18 mg/dL, cTnT ≥ 0.025 ng/mL, and NT-ProBNP ≥ 1,800 pg/mL, creating stages I to IV with scores of 0 to 3 points, respectively. The proportions of patients with stages I, II, III and IV disease were 189 (25%), 206 (27%), 186 (25%) and 177 (23%), and their median OS from diagnosis was 94.1, 40.3, 14, and 5.8 months, respectively (P < .001). This classification system was validated in the other datasets.
  
  
  CONCLUSIONS
  Incorporation of serum FLC-diff into the current staging system improves risk stratification for patients with AL amyloidosis and will help develop risk-adapted therapies for AL amyloidosis.
authors.affiliation: Mayo Clinic, Rochester, MN, USA. kumar.shaji@mayo.edu
authors.forename: Shaji
authors.initials: S
authors.lastname: Kumar
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Hayman
authors.forename: Francis K
authors.initials: FK
authors.lastname: Buadi
authors.forename: Colin
authors.initials: C
authors.lastname: Colby
authors.forename: Kristina
authors.initials: K
authors.lastname: Laumann
authors.forename: Steve R
authors.initials: SR
authors.lastname: Zeldenrust
authors.forename: Nelson
authors.initials: N
authors.lastname: Leung
authors.forename: David
authors.initials: D
authors.lastname: Dingli
authors.forename: Philip R
authors.initials: PR
authors.lastname: Greipp
authors.forename: John A
authors.initials: JA
authors.lastname: Lust
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000097:blood / Q000145:classification* / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis*; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D015996:Survival Rate; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain