Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia

Natali Pflug, Jasmin Bahlo, Tait D. Shanafelt, Barbara F. Eichhorst, Manuela A. Bergmann, Thomas Elter, Kathrin Bauer, Gebhart Malchau, Kari G. Rabe, Stephan Stilgenbauer, Hartmut Döhner, Ulrich Jäger, Michael J. Eckart, Georg Hopfinger, Raymonde Busch, Anna Maria Fink, Clemens Martin Wendtner, Kirsten Fischer, Neil E. Kay, Michael Hallek

Research output: Contribution to journalArticle

170 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)49-62
Number of pages14
JournalBlood
Volume124
Issue number1
DOIs
StatePublished - Jul 3 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Pflug, N., Bahlo, J., Shanafelt, T. D., Eichhorst, B. F., Bergmann, M. A., Elter, T., Bauer, K., Malchau, G., Rabe, K. G., Stilgenbauer, S., Döhner, H., Jäger, U., Eckart, M. J., Hopfinger, G., Busch, R., Fink, A. M., Wendtner, C. M., Fischer, K., Kay, N. E., & Hallek, M. (2014). Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia. Blood, 124(1), 49-62. https://doi.org/10.1182/blood-2014-02-556399