Prognostic value of Ki-67 index, cytology, and growth pattern in mantle-cell lymphoma: Results from randomized trials of the european mantle cell lymphoma network

Eva Hoster, Andreas Rosenwald, Françoise Berger, Heinz Wolfram Bernd, Sylvia Hartmann, Christoph Loddenkemper, Thomas F E Barth, Nicole Brousse, Stefano Pileri, Grzegorz Rymkiewicz, Roman Kodet, Stephan Stilgenbauer, Roswitha Forstpointner, Catherine Thieblemont, Michael Hallek, Bertrand Coiffier, Ursula Vehling-Kaiser, Ŕeda Bouabdallah, Lothar Kanz, Michael PfreundschuhChristian Schmidt, Vincent Ribrag, Wolfgang Hiddemann, Michael Unterhalt, Johanna C. Kluin-Nelemans, Olivier Hermine, Martin H. Dreyling, Wolfram Klapper

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose Mantle-cell lymphoma (MCL) is a rather aggressive B-cell malignancy whose considerable variability of individual outcome is associated with clinical characteristics (MantleCell 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 fromthe EuropeanMCL Younger andMCL Elderly trials,weaimedto 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.

Original languageEnglish
Pages (from-to)1386-1394
Number of pages9
JournalJournal of Clinical Oncology
Volume34
Issue number12
DOIs
Publication statusPublished - Apr 20 2016

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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