Immunophenotypic Landscape and Prognosis of Diffuse Large B-Cell Lymphoma with MYC/BCL2 Double Expression: An Analysis of A Prospectively Immunoprofiled Cohort.

Bogyeong Han,Dae Seog Heo,Yoon Kyung Jeon,Sehui Kim,Tae Min Kim,Jeemin Yim,Jiwon Koh,Jin Ho Paik,Cheol Lee

doi:10.3390/cancers12113305

Abstract

Simple SummaryDiffuse large B-cell lymphoma (DLBCL) with MYC/BCL2 double-expression (DE), a recently proposed poor prognostic group, can be easily identified by immunohistochemistry in routine clinical practice. However, clinical outcomes of DE-DLBCL patients vary immensely after R-CHOP immunochemotherapy and prognostic impact of MYC/BCL2-DE was conflicting according to the cell-of-origin, i.e., between germinal center-B-cell (GCB)- and non-GCB-DLBCLs. This implies the heterogeneity within DE-DLBCLs and emphasizes a need for proper risk stratification to select the patients who require more intensive therapy. By analyzing a prospectively immunoprofiled cohort of consecutively diagnosed DLBCL patients, we confirmed the poor prognostic value of MYC/BCL2-DE in DLBCL patients treated with R-CHOP irrespective of the cell-of-origin and international prognostic index. DE-DLBCLs with a concurrent risk factor, especially, elevated serum lactate dehydrogenase (LDH), had the worst survival and DE-DLBCL patients with normal LDH had clinical outcomes similar to those of non-DE-DLBCL patients. Risk stratification of DE-DLBCL based on serum LDH may guide clinical decision-making for DE-DLBCL patients.Diffuse large B-cell lymphoma (DLBCL) patients with MYC/BCL2 double expression (DE) show poor prognosis and their clinical outcomes after R-CHOP therapy vary immensely. We investigated the prognostic value of DE in aggressive B-cell lymphoma patients (n = 461), including those with DLBCL (n = 417) and high-grade B-cell lymphoma (HGBL; n = 44), in a prospectively immunoprofiled cohort. DE was observed in 27.8% of DLBCLs and 43.2% of HGBLs (p = 0.058). DE-DLBCL patients were older (p = 0.040) and more frequently exhibited elevated serum LDH levels (p = 0.002), higher international prognostic index (IPI; p = 0.042), non-germinal-center B-cell phenotype (p < 0.001), and poor response to therapy (p = 0.042) compared to non-DE-DLBCL patients. In R-CHOP-treated DLBCL patients, DE status predicted poor PFS and OS independently of IPI (p < 0.001 for both). Additionally, in DE-DLBCL patients, older age (>60 years; p = 0.017), involvement of ≥2 extranodal sites (p = 0.021), bone marrow involvement (p = 0.001), high IPI (p = 0.017), CD10 expression (p = 0.006), poor performance status (p = 0.028), and elevated LDH levels (p < 0.001) were significantly associated with poor OS. Notably, DE-DLBCL patients with normal LDH levels exhibited similar PFS and OS to those of patients with non-DE-DLBCL. Our findings suggest that MYC/BCL2 DE predicts poor prognosis in DLBCL. Risk stratification of DE-DLBCL patients based on LDH levels may guide clinical decision-making for DE-DLBCL patients.

Highlights

Significant progress in the classification of aggressive B-cell lymphoma has been made in the last decade [1,2]
We investigated the clinicopathological implications of double expression (DE) status in diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) patients and the potential of the risk stratification strategy for DE-DLBCL patients treated with R-CHOP
We found that DE status was a poor prognostic factor in DLBCL patients independently of international prognostic index (IPI), consistent with previous studies showing an association of DE

Summary

Introduction

Significant progress in the classification of aggressive B-cell lymphoma has been made in the last decade [1,2]. Common entities include diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), and high-grade B-cell lymphoma (HGBL) [1,2]. Except for BL, DLBCLs and HGBLs are characterized by heterogeneous pathological, genetic, and clinical features, increasing the need for more accurate disease clarification and prognostication. Evidence from retrospective studies shows that DH lymphoma patients receiving intensive treatment exhibit a better clinical outcome than patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) [6,7,8]. DH lymphoma should be considered as a distinct entity according to the revised 4th World Health Organization (WHO) classification of lymphoma [9]

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