Meta-Analysis of the Prognostic Significance of BCL6+/CD10+ Mantle Cell Lymphoma
Authors: Park Daniel , Jeon Won Jin , Joung Bowon , Pham Bryan , Hino Christopher , Lee Jae , Yang Chieh , Chong Esther G , Mehta Akhil , Moon Jin Hyun , Shields Andrea , Nguyen Anthony , Brothers Joel , Liu Yan , Akhtari Mojtaba , Zhang Ke K , Cao Huynh , Castillo Dani Ran 
Published: December 2023

Background:
Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL), classically characterized by the translocation of t(11;14). MCL is typically CD10 negative, often attributed to its pre-germinal nature arising from naïve B cells. Increasing cases of CD10+ MCL suggest the possibility of germinal center-derived pathology. Moreover, a unique and rarer BCL6+/CD10+ immunophenotype has been reported in the literature and warrants investigation into its clinicopathologic significance. This meta-analysis was conducted to further investigate the relationship between MCL immunophenotypes and their clinical outcomes.
Methods:
A meta-analysis was conducted to investigate the relationship between MCL immunophenotypes and clinical outcomes. Endpoints collected included clinical features, overall survival (OS), morphology, immunophenotypes , Ki67%, and cytologic variants. OS data was pooled from multiple studies and assessed using the R programming package survival. A log-rank test was performed to compare OS. The mean differences in OS between BCL6+ and BCL6- MCL for individual studies were calculated and combined to minimize the batch effects. If individual Ki67 indexes were not available, the standard deviation (SD) of the mean difference was calculated based on normal distribution and the sample size of the particular study. The summary statistics across all studies was calculated by averaging all mean differences and pooling individual SDs. The correlations between CD10 & BCL6, BCL6 & blastoid morphology, and BCL6 & SOX11 were tested using Fisher's exact test. Statistical significance was determined by setting the alpha (α) level at 0.05.
Results:
The meta-analysis included 537 patients (425 males and 112 females). The median age of diagnosis in CD10+ and CD10- MCL was 69 and 61.5 years old, respectively. There were 70 CD10+, 467 CD10-, and 22 BCL6+/CD10+ patients. BCL6 positivity had an odds ratio of 5.11 (95% CI [2.49, 10.46]; p=0.00002386) for CD10 positivity compared to CD10 negativity. The subgroup analysis showed a higher frequency of blastoid/pleomorphic/small morphology variants in BCL6+/CD10+ MCL. Correlation analysis between BCL6 positivity and blastoid/pleomorphic/small morphology did not demonstrate significant correlation (p=0.2423). However, positive correlation was seen between BCL6 and SOX11 (p=0.013). BCL6+ MCL was associated with an inferior median OS compared to BCL6- MCL (BCL6+: 14 months vs. BCL6-: 43 months; p=0.01). Furthermore, BCL6+/CD10+ co-expression was associated with an inferior median OS compared to BCL6-/CD10+ MCL (BCL6+/CD10+: 20 months vs. BCL6-/CD10+: 55 months; p&lt;0.01).
Conclusion:
Based on the analysis, it was found that BCL6 expression positivity negatively impacts overall survival (OS) in MCL, regardless of CD10 expression. The higher Ki67% observed in BCL6 expression positivity compared to BCL6 negativity suggests the prognostic value of the BCL6 immunophenotype in MCL. Additionally, BCL6 expression was found to be correlated with CD10 and SOX11 expression, indicating the clinical significance of these variables when combined with BCL6 positivity. It is suggested that prognostic scoring systems adjusted for BCL6 could provide further insights into the prognostic categorization, management, classification, and future tailored treatment of MCL variants.