TY - JOUR
T1 - Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia
AU - Pflug, Natali
AU - Bahlo, Jasmin
AU - Shanafelt, Tait D.
AU - Eichhorst, Barbara F.
AU - Bergmann, Manuela A.
AU - Elter, Thomas
AU - Bauer, Kathrin
AU - Malchau, Gebhart
AU - Rabe, Kari G.
AU - Stilgenbauer, Stephan
AU - Döhner, Hartmut
AU - Jäger, Ulrich
AU - Eckart, Michael J.
AU - Hopfinger, Georg
AU - Busch, Raymonde
AU - Fink, Anna Maria
AU - Wendtner, Clemens Martin
AU - Fischer, Kirsten
AU - Kay, Neil E.
AU - Hallek, Michael
PY - 2014/7/3
Y1 - 2014/7/3
N2 - In addition to clinical staging, a number of biomarkers predicting overall survival (OS) have been identified in chronic lymphocytic leukemia (CLL). The multiplicity of markers, limited information on their independent prognostic value, and a lack of understanding of how to interpret discordant markers are major barriers to use in routine clinical practice. We therefore performed an analysis of 23 prognostic markers based on prospectively collected data from 1948 CLL patients participating in phase 3 trials of the German CLL Study Group to develop a comprehensive prognostic index. A multi variable Cox regression model identified 8 independent predictors of OS: sex, age, ECOG status, del(17p), del(11q), IGHV mutation status, serum b2-microglobulin, and serum thymidine kinase. Using a weighted grading system, a prognostic index was derived that separated 4 risk categories with 5-year OS ranging from 18.7% to 95.2% and having a C-statistic of 0.75. The index stratified OS within all analyzed subgroups, including all Rai/Binet stages. The validity of the index was externally confirmed in a series of 676 newly diagnosed CLL patients from Mayo Clinic. Using this multistep process including external validation, we developed a comprehensive prognostic index with high discriminatory power and prognostic significance on the individual patient level.
AB - In addition to clinical staging, a number of biomarkers predicting overall survival (OS) have been identified in chronic lymphocytic leukemia (CLL). The multiplicity of markers, limited information on their independent prognostic value, and a lack of understanding of how to interpret discordant markers are major barriers to use in routine clinical practice. We therefore performed an analysis of 23 prognostic markers based on prospectively collected data from 1948 CLL patients participating in phase 3 trials of the German CLL Study Group to develop a comprehensive prognostic index. A multi variable Cox regression model identified 8 independent predictors of OS: sex, age, ECOG status, del(17p), del(11q), IGHV mutation status, serum b2-microglobulin, and serum thymidine kinase. Using a weighted grading system, a prognostic index was derived that separated 4 risk categories with 5-year OS ranging from 18.7% to 95.2% and having a C-statistic of 0.75. The index stratified OS within all analyzed subgroups, including all Rai/Binet stages. The validity of the index was externally confirmed in a series of 676 newly diagnosed CLL patients from Mayo Clinic. Using this multistep process including external validation, we developed a comprehensive prognostic index with high discriminatory power and prognostic significance on the individual patient level.
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U2 - 10.1182/blood-2014-02-556399
DO - 10.1182/blood-2014-02-556399
M3 - Article
C2 - 24797299
AN - SCOPUS:84903971364
SN - 0006-4971
VL - 124
SP - 49
EP - 62
JO - Blood
JF - Blood
IS - 1
ER -