Blood Journal
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First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia

  1. Barbara F. Eichhorst1,
  2. Raymonde Busch2,
  3. Stephan Stilgenbauer3,
  4. Martina Stauch4,
  5. Manuela A. Bergmann5,
  6. Matthias Ritgen6,
  7. Nicole Kranzhöfer7,
  8. Robert Rohrberg8,
  9. Ulrike Söling9,
  10. Oswald Burkhard10,
  11. Anne Westermann1,
  12. Valentin Goede1,
  13. Carmen D. Schweighofer1,
  14. Kirsten Fischer1,
  15. Anna-Maria Fink1,
  16. Clemens M. Wendtner1,
  17. Günter Brittinger11,
  18. Hartmut Döhner3,
  19. Bertold Emmerich12,
  20. Michael Hallek1, and
  21. the German CLL Study Group (GCLLSG)
  1. 1Department I of Internal Medicine, Centre of Integrated Oncology Köln Bonn, University of Cologne, Cologne;
  2. 2Institute of Medical Statistics and Epidemiology, Technical University, Munich;
  3. 3Department of Internal Medicine III, University of Ulm, Ulm;
  4. 4Private practice, Kronach;
  5. 5Department of Internal Medicine III, University of Munich, Munich;
  6. 6Department of Internal Medicine II, University of Schleswig-Holstein, Kiel;
  7. 7Department of Internal Medicine, University of Saarland, Homburg;
  8. 8Private practice, Halle;
  9. 9Private practice, Kassel;
  10. 10Private practice, Worms;
  11. 11Department of Hematology, University of Duisburg-Essen, Essen; and
  12. 12Department of Internal Medicine Innenstadt, Ludwig-Maximilians-University of Munich, Munich, Germany
  1. Results from an interim analysis were presented, in part, at the 45th Annual Meeting of the American Society of Hematology, San Diego, CA, December 6-9, 2003. Preliminary results from the final analysis were presented, in part, at the 14th International CLL Workshop, London, United Kingdom, September 14-16, 2007, as well as at the 49th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 8-11, 2007.


Although chronic lymphocytic leukemia (CLL) is a disease of elderly patients, subjects older than 65 years are heavily underrepresented in clinical trials. The German CLL study group (GCLLSG) initiated a multicenter phase III trial for CLL patients older than 65 years comparing first-line therapy with fludarabine with chlorambucil. A total of 193 patients with a median age of 70 years were randomized to receive fludarabine (25 mg/m2 for 5 days intravenously, every 28 days, for 6 courses) or chlorambucil (0.4 mg/kg body weight [BW] with an increase to 0.8 mg/kg, every 15 days, for 12 months). Fludarabine resulted in a significantly higher overall and complete remission rate (72% vs 51%, P = .003; 7% vs 0%, P = .011). Time to treatment failure was significantly shorter in the chlorambucil arm (11 vs 18 months; P = .004), but no difference in progression-free survival time was observed (19 months with fludarabine, 18 months with chlorambucil; P = .7). Moreover, fludarabine did not increase the overall survival time (46 months in the fludarabine vs 64 months in the chlorambucil arm; P = .15). Taken together, the results suggest that in elderly CLL patients the first-line therapy with fludarabine alone does not result in a major clinical benefit compared with chlorambucil. This trial is registered with under identifier ISRCTN 36294212.

  • Submitted February 20, 2009.
  • Accepted June 27, 2009.
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