TY - JOUR
T1 - Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements
AU - Kumar, Shaji
AU - Dispenzieri, Angela
AU - Lacy, Martha Q.
AU - Hayman, Suzanne R.
AU - Buadi, Francis K.
AU - Colby, Colin
AU - Laumann, Kristina
AU - Zeldenrust, Steve R.
AU - Leung, Nelson
AU - Dingli, David
AU - Greipp, Philip R.
AU - Lust, John A.
AU - Russell, Stephen J.
AU - Kyle, Robert A.
AU - Rajkumar, S. Vincent
AU - Gertz, Morie A.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/3/20
Y1 - 2012/3/20
N2 - Purpose: 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. Patients and 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. Conclusion: 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.
AB - Purpose: 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. Patients and 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. Conclusion: 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.
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U2 - 10.1200/JCO.2011.38.5724
DO - 10.1200/JCO.2011.38.5724
M3 - Article
C2 - 22331953
AN - SCOPUS:84860643971
SN - 0732-183X
VL - 30
SP - 989
EP - 995
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -