Clinicopathological characteristics, genetic aberrations, and optimized treatment strategies in double-hit and triple-hit lymphoma: a multi-center cohort study
Year: 2025
Type: article
Study design: Observational Study
Abstract: High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements constitutes a distinct clinicopathological entity characterized by aggressive behavior, inherent resistance to conventional immunochemotherapy, and suboptimal clinical outcomes. Within our cohort, MYC/BCL2 rearrangements defined double-hit lymphoma (DHL), MYC/BCL6 as DHL-BCL6, and concurrent MYC/BCL2/BCL6 as triple-hit lymphoma (THL). Here, we delineated the clinical characteristics and genetic aberrations of 112 DHL/THL patients to investigate the factors influencing lymphoma relapse and optimize treatment strategies. Compared to 80 DHL-BCL6 patients, DHL/THL manifested distinct features, including an increased prevalence of the germinal center B-cell-like subtype and co-expression of MYC/BCL2, and demonstrated significant associations with abbreviated progression-free and overall survival. Univariate and multivariate analyses identified Ann Arbor stage and serum lactate dehydrogenase elevation as independent prognostic determinants. Therapeutic intensification employing R-DA-EDOCH was correlated with enhanced survival outcomes, while consolidative autologous stem cell transplantation significantly improved prognosis in patients who achieved remission after first-line immunochemotherapy. Regarding genetic aberrations, oncogenic mutations were detected in 102 evaluable patients. EZH2 mutation occurred more frequently in DHL/THL, while TNFRSF14 mutation exhibited greater prevalence in THL. The EZB genotype was predominantly observed in DHL/THL patients, and those with TP53 abnormalities exhibited a further diminished prognosis. In terms of the immune microenvironment, the depleted lymphoma microenvironment (LME-DP) subtype, characterized by diminished immune cell infiltration, demonstrated a propensity for increased frequency in DHL/THL patients. Collectively, these findings advance the comprehensive understanding of DHL/THL pathobiology, underscoring the imperative for novel targeted agents and therapeutic approaches.
Source: Molecular Biomedicine
Authors: Yi-Ge Shen, Meng-Meng Ji, Qing Shi, Xiao-Lei Wei, Lei Fan, Ting-Bo Liu, Yao Liu, Li-Hua Dong, Ai-Bin Liang, Liang Huang, Hui Zhou, Hong-Hui Huang, Shen-Miao Yang, Xiao-Bo Wang, Yu-Yang Tian, Zun-Min Zhu, Ou Bai, Fei Li, Wen-Yu Shi, Bin Xu, Xin Wang, Ke-Qian Shi, Wei Tang, Hong-Mei Yi, Si-Yuan Chen, Zhong Zheng, Shu Cheng, Peng-Peng Xu, Wei-Li Zhao, Li Wang
Institutions: Shanghai Jiao Tong University, Ruijin Hospital, Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Nanfang Hospital, Southern Medical University, Jiangsu Province Hospital, Nanjing Medical University, Fujian Medical University, Union Hospital, Chongqing University, Chongqing Cancer Hospital, Zhengzhou University, Henan Cancer Hospital, Tongji University, Tongji Hospital, Huazhong University of Science and Technology, Central South University, Hunan Cancer Hospital, Renji Hospital, Peking University, Peking University People's Hospital, Shandong University, Second Affiliated Hospital of Dalian Medical University, Shandong Provincial Hospital, Henan Provincial People's Hospital, First Hospital of Jilin University, First Affiliated Hospital of Nanchang University, Affiliated Hospital of Nantong University, First Affiliated Hospital of Xiamen University, First People's Hospital of Yunnan Province
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,590
OpenAlex ID: W4417147343