PURPOSE: Mantle-cell lymphoma (MCL) is a rather aggressive B-cell malignancy whose considerable variability of individual outcome is associated with clinical characteristics (Mantle Cell Lymphoma International Prognostic Index [MIPI]). The Ki-67 index is a strong independent prognostic factor; however, the biologic MIPI (MIPI-b) distinguishes only two groups, which does not appropriately depict the clinical heterogeneity. By using the cohort from the European MCL Younger and MCL Elderly trials, we aimed to evaluate the additional prognostic impact of cytology and growth pattern and to improve risk stratification with the Ki-67 index and MIPI. PATIENTS AND METHODS: Diagnostic tumor biopsies were reviewed by the European Mantle Cell Lymphoma Pathology Panel to determine Ki-67 index by using published guidelines, cytology, and growth pattern. We evaluated prognostic effects for overall survival (OS) by Cox regression. For the cohort used for MIPI-b development (German Low-Grade Lymphoma Study Group [GLSG] 1996 and GLSG2000), we checked whether the equally weighted combination of Ki-67 index (dichotomized at the validated 30% cutoff) and MIPI risk groups was adequate and compared the prognostic power of this modified combination to MIPI and MIPI-b for the MCL Younger/MCL Elderly cohort. RESULTS: The Ki-67 index was assessed in 508 of 832 patients (median age, 62 years). Blastoid cytology was associated with inferior OS independently of MIPI but not independently of the Ki-67 index. Growth pattern was not independently prognostic. The modified combination of the Ki-67 index and MIPI separated four groups with 5-year OS: 85%, 72%, 43%, and 17% (P < .001) and was more discriminative than MIPI and MIPI-b. CONCLUSION: Using the Ki-67 index is superior to using cytology and growth pattern as prognostic factors in MCL. The modified combination of the Ki-67 index and MIPI showed a refined risk stratification, reflecting their strong complementary prognostic effects while integrating the most relevant prognostic factors available in clinical routine.

Eva Hoster Roswitha Forstpointner Christian Schmidt Wolfgang Hiddemann Michael Unterhalt and Martin H Dreyling University Hospital Munich; Eva Hoster University of Munich Munich; Andreas Rosenwald University of Würzburg Würzburg; Heinz Wolfram Bernd University Hospital Schleswig Holstein Lübeck; Sylvia Hartmann University Hospital of Frankfurt Frankfurt am Main; Christoph Loddenkemper University Hospital Berlin Charité; Christoph Loddenkemper Pathologie PathoTres Berlin; Thomas F E Barth University Medical Center Ulm; Stephan Stilgenbauer University of Ulm Ulm; Michael Hallek Universität zu Köln Köln; Ursula Vehling Kaiser Tagesklinik Hämatologie Onkologie Landshut; Lothar Kanz University of Tübingen Tübingen; Michael Pfreundschuh Universitätsklinik des Saarlandes Homburg; Wolfram Klapper University of Kiel Kiel Germany; Françoise Berger LYSA Group; Nicole Brousse Hopital Necker; Catherine Thieblemont Hôpital Saint Louis; Olivier Hermine University Paris Descartes; Olivier Hermine Université Sorbonne Paris Cité Paris; Bertrand Coiffier Centre Hospitalier Lyon Sud Pierre Bénite; Réda Bouabdallah Service d'Hématologie Marseille; Vincent Ribrag Institut Gustave Roussy Villejuif France; Stefano Pileri University of Bologna Bologna Italy; Grzegorz Rymkiewicz The Maria Skłodowska Curie Memorial Cancer Center and Institute of Oncology Warsaw Poland; Roman Kodet Charles University Prague Czech Republic; and Johanna C Kluin Nelemans University of Groningen Groningen The Netherlands

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