Unveiling the prognostic significance of BCL6+/CD10+ mantle cell lymphoma: A systematic analysis.

person Dan Ran Castillo Division of Medical Oncology and Hematology, Loma Linda University School of Medicine, Loma Linda, CA info_outline Dan Ran Castillo, Daniel Park, Won Jin Jeon, Esther G Chong, Bowon Floyd Joung, Jin Hyun Floyd Moon, Bryan Pham, Jae Lee, Zeeshan Siddiqui, Anthony Loc Nguyen, Ke Kurt Zhang, Huynh Le Cao

Authors person Dan Ran Castillo Division of Medical Oncology and Hematology, Loma Linda University School of Medicine, Loma Linda, CA info_outline Dan Ran Castillo, Daniel Park, Won Jin Jeon, Esther G Chong, Bowon Floyd Joung, Jin Hyun Floyd Moon, Bryan Pham, Jae Lee, Zeeshan Siddiqui, Anthony Loc Nguyen, Ke Kurt Zhang, Huynh Le Cao Organizations Division of Medical Oncology and Hematology, Loma Linda University School of Medicine, Loma Linda, CA, Department of Internal Medicine school of Medicine, University of California San Francisco, Fresno, CA, Loma Linda University Department of Internal Medicine, Loma Linda, CA, Division of Medical Oncology and Hematology, Loma Linda University of Medicine, Loma Linda, CA, Internal medicine, Loma Linda University health, Loma Linda, CA, Loma Linda University, School of Medicine, Loma Linda, CA, UC San Diego Moores Cancer Center, Loma Linda, CA, Department of Nutrition, Texas A&M university, College Station, Houston, TX, Department of Oncology/Hematology, Loma Linda University Medical Center, Loma Linda, CA Abstract Disclosures Research Funding No funding received None. Background: Mantle cell lymphoma (MCL) is heterogenetic B-cell neoplasm that characterized by the presence of the IgH/CCND1 translocation. The significance of CD10 expression in MCL is not fully understood. The co-expression of CD10 and BCL6 in MCL is rare requiring further investigation to determine its clinical significance. This meta-analysis aims to examine the relationship between MCL variants and their cellular behaviors and clinical outcomes. Methods: A search of the GDC and dbGaP database was conducted using the PICOS model and PRISMA guidelines to retrieve survival data. Overall survival (OS) data was pooled from multiple studies and analyzed using the R programming package survival and a log-rank test was performed to compare OS. Mean differences between BCL6+ vs. BCL6- for individual studies were calculated and combined to minimize batch effects. Summary statistics across studies were obtained by averaging mean differences and pooling individual standard deviations. The correlation between CD10 and BCL6 was tested using Fisher's exact test, with a significance level of 0.05. Results: The analysis included a total of 537 patients (425 males and 112 females), with a median age at diagnosis of 69 years in CD10+ MCL and 61.5 years in CD10- MCL. Out of the 537 patients, 70 were CD10+ positive, and BCL6 positivity had an odds ratio of 5.11 [95% CI [2.49, 10.46]; p = 0.0000286) for CD10 positivity compared to CD10 negativity. The subgroup analysis revealed a higher frequency of blastoid/pleomorphic/small variants in BCL6+/CD10+ MCL. BCL6 positivity was associated with worse OS, independent of CD10 expression (median OS of 14 months in BCL6+ MCL vs. 43 months in BCL6- MCL; p = 0.01). The co-expression of BCL6 and CD10 was associated with a shorter median OS (22 months in BCL6+CD10+ vs. 55 months in BCL6-CD10+, p = 0.01) and significantly higher mitotic index (Ki67%) compared to BCL6-/CD10+ MCL (mean Ki67% of 63.13 ± 19.45% vs. 45 ± 21.69%, p < 0.01). The forest plot analysis showed that BCL6 expression was correlated with a significantly higher Ki67% (difference of 24.29; p = 0.0094). Conclusions: Our meta-analysis found that BCL6 expression correlates with CD10 positivity in MCL variants and has a negative impact on prognosis, independent of CD10 expression. Higher Ki67% levels in BCL6+ MCL compared to BCL6- MCL support the prognostic value of the BCL6+ immunophenotype in MCL variants. Prognostic scoring systems adjusted for BCL6 expression should be incorporated into MCL management. Targeted therapies against BCL6 may offer potential treatment options for MCL subtypes. CD10+ n = 70 CD10- N = 467 Male/Female 1.5:1(42/28) 4.6:1(383/84) Median Age (years) 69 61.5 Classic 47.1% (33) 74.7% (374) Blastoid/Pleomorphic/Small 48.6% (34) 16.8% (79) BCL6+ 22 112 BCL6- 41 349 Ki67% difference BCL6+ vs BCL6-: 24.29 (5.97-42.62), p = 0.0094 Median OS in BCL6+/CD10+ 22 p = 0.01 Median OS in BCL6-/CD10+ 55