Submitted October 5, 2007
Accepted November 30, 2007
Ki-67 predicts outcome in advanced stage mantle cell lymphoma patients treated with anti-CD20 immunochemo-therapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group
Olaf Determann, Eva Hoster, German Ott, Heinz Wolfram Bernd, Christoph Loddenkemper, Martin Leo Hansmann, Thomas E .F. Barth, Michael Unterhalt, Wolfgang Hiddemann, Martin Dreyling, and Wolfram Klapper*
Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Department of Internal Medicine III, University of Munich, Munich, Germany
Department of Clinical Pathology, Robert-Bosch-Krankenhaus Stuttgart, Stuttgart, Germany
Department of Pathology, University Hospital Schleswig-Holstein, Campus Lubeck, Lubeck, Germany
Department of Pathology, University Hospital Charite, Campus Benjamin-Franklin, Berlin, Germany
Department of Pathology, University of Frankfurt, Frankfurt, Germany
Department of Pathology, University of Ulm, Ulm, Germany
* Corresponding author; email: wklapper{at}path.uni-kiel.de.
Clinical outcome of mantle cell lymphoma (MCL) is highly heterogeneous. Tumor cell proliferation as assessed by the Ki-67 index has been shown to yield prognostic information on MCL in many studies using heterogeneously treated patient cohorts. The prognostic value of the Ki-67 index in patients treated with anti-CD20 therapy has not been studied so far. We analyzed the Ki-67 index at primary diagnosis in 249 advanced stage MCL patients treated within randomized trials. Ki-67 showed high prognostic relevance for overall survival (relative risk 1.27 for 10% higher Ki-67, p<0.0001), also independently from clinical prognostic factors. The three groups with different Ki-67 index of <10%, >=10 to <30%, and >=30% showed significantly different overall survival in patients treated with CHOP (p=0.0002) as well as in patients treated with CHOP in combination with anti-CD20 therapy (R-CHOP, p=0.0126). Thus, the Ki-67 index remains an important prognostic marker in the era of anti-CD20 therapy. The European MCL study is registered at
www.ClinicalTrials.gov as #NCT00016887.
