Universität zu Köln

Pflug, Natali, Bahlo, Jasmin, Shanafelt, Tait D., Eichhorst, Barbara F., Bergmann, Manuela A., Elter, Thomas, Bauer, Kathrin, Malchau, Gebhart, Rabe, Kari G., Stilgenbauer, Stephan, Doehner, Hartmut, Jaeger, Ulrich, Eckart, Michael J., Hopfinger, Georg, Busch, Raymonde, Fink, Anna-Maria, Wendtner, Clemens-Martin, Fischer, Kirsten, Kay, Neil E. and Hallek, Michael (2014). Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia. Blood, 124 (1). S. 49 - 63. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

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Abstract

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 multivariable Cox regression model identified 8 independent predictors of OS: sex, age, ECOG status, del(17p), del(11q), IGHV mutation status, serum beta(2)-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. The studies were registered as follows: CLL1 trial (NCT00262782, http://clinicaltrials.gov), CLL4 trial (ISRCTN 75653261, http://www.controlled-trials.com), and CLL8 trial (NCT00281918, http://clinicaltrials.gov).

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pflug, Natali UNSPECIFIED UNSPECIFIED UNSPECIFIED Bahlo, Jasmin UNSPECIFIED UNSPECIFIED UNSPECIFIED Shanafelt, Tait D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichhorst, Barbara F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergmann, Manuela A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Elter, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauer, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Malchau, Gebhart UNSPECIFIED UNSPECIFIED UNSPECIFIED Rabe, Kari G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stilgenbauer, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Doehner, Hartmut UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaeger, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckart, Michael J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hopfinger, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Busch, Raymonde UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Anna-Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Wendtner, Clemens-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Kirsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Kay, Neil E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-434097
DOI:	10.1182/blood-2014-02-556399
Journal or Publication Title:	Blood
Volume:	124
Number:	1
Page Range:	S. 49 - 63
Date:	2014
Publisher:	AMER SOC HEMATOLOGY
Place of Publication:	WASHINGTON
ISSN:	1528-0020
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SERUM THYMIDINE KINASE; PREVIOUSLY UNTREATED PATIENTS; PHASE-II TRIAL; MUTATIONAL STATUS; PREDICTIVE-VALUE; SURVIVAL; FLUDARABINE; RITUXIMAB; NOTCH1; CLL Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43409