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 < .001), also independently from clinical prognostic factors. The 3 groups with different Ki-67 index of less than 10%, 10% to less than 30%, and 30% or more showed significantly different overall survival in patients treated with CHOP (P ‫؍‬ .001) as well as in patients treated with CHOP in combination with anti-CD20 therapy (R-CHOP, P ‫؍‬ .013). 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. IntroductionMantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (B-NHL) with a median overall survival (OS) of the patients of 3 to 5 years. 1 Clinical outcome of this disease is highly heterogeneous. 2 Since MCL patients often present at an advanced age and treatment strategies differ in terms of their potential side effects, several attempts have been made to identify high-and low-risk patients for a risk-adapted therapy. [2][3][4][5] In contrast to many other B-NHLs, increased proliferation of the tumor cells has been shown to be distinctly correlated with shorter survival in MCL. Thus, the proliferation index as assessed by the percentage of Ki-67 positive cells represents an important prognostic marker in several studies. 2,6,7 However, the studies published so far aiming at the prognostic value of Ki-67 analyzed patients with heterogeneous therapeutic regimens that were not treated within prospective randomized trials. 2,6,7 The addition of anti-CD20 (rituximab) to the chemotherapy protocols improved the outcome and might have changed the risk-factor profile of diffuse large B-cell lymphomas (DLBCL). Thus, BCL2 expression, a marker for unfavorable outcome in DLBCL, might lose its predictive value in DLBCL patients treated with rituximab. 8 The introduction of rituximab into the treatment protocols for MCL has improved the outcome substantially. 9 However, to date it is uncertain, whether proliferation can predict outcome in MCL treated with rituximab. We studied the tumor-cell proliferation rate in 249 newly diagnosed patients with advanced-stage MCL treated within the randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group (GLSG; a list of the members of the study group is available as Document S1 on the Blood website; see the Supplemental Materials link at the top of the online article). Methods PatientsLocal ethics committees of the participating centers approved the study protocol, and written infor...

Mantle cell lymphoma (MCL) has a heterogeneous clinical course and is mainly an aggressive B cell non-Hodgkin lymphoma; however, there are some indolent cases The Ki-67 index, defined by the percentage of Ki-67-positive lymphoma cells on histopathological slides, has been shown to be a very powerful prognostic biomarker. The pathology panel of the European MCL Network evaluated methods to assess the Ki-67 index including stringent counting, digital image analysis, and estimation by eyeballing. Counting of 2×500 lymphoma cells is the gold standard to assess the Ki-67 index since this value has been shown to predict survival in prospective randomized trials of the European MCL Network. Estimation by eyeballing and digital image analysis showed a poor concordance with the gold standard (concordance correla-J Hematopathol (2009)

The presence of sclerosis within the lymphoma is a marker of poor overall survival that is independent of the FLIPI. The quantification of macrophage or absolute T-cell content, grading, and proliferation are of no help in predicting the outcome of FL. Future studies need to identify surrogate markers for the prognostic immune signatures identified by gene expression profiling. Most importantly, new prognostic markers need to be confirmed in patients treated within prospective trials.