Eva Hoster1, Andreas Rosenwald2, Françoise Berger2, Heinz-Wolfram Bernd2, Sylvia Hartmann2, Christoph Loddenkemper2, Thomas F E Barth2, Nicole Brousse2, Stefano Pileri2, Grzegorz Rymkiewicz2, Roman Kodet2, Stephan Stilgenbauer2, Roswitha Forstpointner2, Catherine Thieblemont2, Michael Hallek2, Bertrand Coiffier2, Ursula Vehling-Kaiser2, Réda Bouabdallah2, Lothar Kanz2, Michael Pfreundschuh2, Christian Schmidt2, Vincent Ribrag2, Wolfgang Hiddemann2, Michael Unterhalt2, Johanna C Kluin-Nelemans2, Olivier Hermine2, Martin H Dreyling2, Wolfram Klapper2. 1. 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. eva.hoster@med.uni-muenchen.de. 2. 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.
Abstract
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.
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.
Authors: Jeff D Wang; Samuel G Katz; Elizabeth A Morgan; David T Yang; Xueliang Pan; Mina L Xu Journal: Hum Pathol Date: 2019-08-16 Impact factor: 3.466
Authors: Stephen E Spurgeon; Brian G Till; Peter Martin; Andre H Goy; Martin P Dreyling; Ajay K Gopal; Michael LeBlanc; John P Leonard; Jonathan W Friedberg; Lawrence Baizer; Richard F Little; Brad S Kahl; Mitchell R Smith Journal: J Natl Cancer Inst Date: 2016-12-31 Impact factor: 13.506
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Authors: Hilka Rauert-Wunderlich; Anja Mottok; David W Scott; Lisa M Rimsza; German Ott; Wolfram Klapper; Michael Unterhalt; Hanneke C Kluin-Nelemans; Olivier Hermine; Sylvia Hartmann; Christoph Thorns; Grzegorz Rymkiewicz; Harald Holte; Martin Dreyling; Eva Hoster; Andreas Rosenwald Journal: Br J Haematol Date: 2018-08-10 Impact factor: 6.998
Authors: Diego Villa; Laurie H Sehn; Kerry J Savage; Cynthia L Toze; Kevin Song; Wendie D den Brok; Ciara L Freeman; David W Scott; Alina S Gerrie Journal: Blood Adv Date: 2020-08-11