Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.638757
Keywords
diffuse large B-cell lymphoma; single nodal; single extranodal; serum lactate dehydrogenase; gene mutations; tumor microenvironment
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Funding
- National Natural Science Foundation of China [81830007, 82070204]
- Shanghai Municipal Education Commission Gaofeng Clinical Medicine [20152206, 20152208]
- Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine [DLY201601]
- Clinical Research Plan of SHDC [2020CR1032B]
- Chang Jiang Scholars Program
- Samuel Waxman Cancer Research Foundation
- Foundation of National Facility for Translational Medicine (Shanghai) [TMSK-2020-115]
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The clinical and molecular characteristics of localized diffuse large B-cell lymphoma with single nodal or single extranodal involvement in the rituximab era are complex and not fully understood. Analysis of clinical features, genetic aberrations, and tumor immunophenotype can guide personalized treatment for localized DLBCL in the future.
The clinical and molecular characteristics of localized diffuse large B-cell lymphoma (DLBCL) with single nodal (SN) or single extranodal (SE) involvement remain largely elusive in the rituximab era. The clinical data of 181 patients from a retrospective cohort and 108 patients from a phase 3 randomized trial NHL-001 (NCT01852435) were reviewed. Meanwhile, genetic aberrations, gene expression pattern, and tumor immunophenotype profile were revealed by DNA and RNA sequencing of 116 and 53 patients, respectively. SE patients showed similar clinicopathological features as SN patients, except for an increased percentage of low-intermediate risk in the National Comprehensive Cancer Network-International Prognostic Index. According to the molecular features, increased MPEG1 mutations were observed in SN patients, while SE patients were associated with upregulation of TGF-beta signaling pathway and downregulation of T-cell receptor signaling pathway. SE patients also presented immunosuppressive status with lower activity of killing of cancer cells and recruiting dendritic cells. Extranodal involvement had no influence on progression-free survival (PFS) or overall survival (OS) in localized DLBCL. Serum lactate dehydrogenase > 3 upper limit of normal was an independent adverse prognostic factor for OS, and ATM mutations were related to inferior PFS. Although the overall prognosis is satisfactory, specific clinical, genetic, and microenvironmental factors should be considered for future personalized treatment in localized DLBCL.
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