Clinicopathological characteristics, genetic aberrations, and optimized treatment strategies in double-hit and triple-hit lymphoma: a multi-center cohort study

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.

Authors

Institutions

Publication Details

Journal
Molecular Biomedicine
Published
2025-12-09
DOI
https://doi.org/10.1186/s43556-025-00346-8
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Clinicopathological characteristics, genetic aberrations, and optimized treatment strategies in double-hit and triple-hit lymphoma: a multi-center cohort study

Qing Shi, Honghui Huang, Zhong Zheng, Yige Shen et al.
Molecular Biomedicine
Lymphoma Diagnosis and Treatment
article

Clinicopathological characteristics, genetic aberrations, and optimized treatment strategies in double-hit and triple-hit lymphoma: a multi-center cohort study

Qing Shi, Honghui Huang, Zhong Zheng, Yige Shen, Wenyu Shi, Zunmin Zhu, Weili Zhao, Mengmeng Ji, Tingbo Liu, Keqing Shi, Ou Bai, Shenmiao Yang, Bin Xu, Hongmei Yi, Shu Cheng, Fei Li, Xin Wang, Li Wang, Siyuan Chen, Yao Liu, Liang Huang, Wei Tang, Lei Fan, Xiaolei Wei, Lihua Dong, Pengpeng Xu, Yuyang Tian, Xiaobo Wang, Aibin Liang, Hui Zhou
article en

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.

Molecular BiomedicineVol. 6(1)
Tongji University (CN), Fujian Medical University (CN), Central South University (CN), Nanchang University (CN), Shandong University (CN), Chongqing University (CN), Shanghai Jiao Tong University (CN), Dalian Medical University (CN), Jilin University (CN), Nantong University (CN), Peking University (CN), Renji Hospital (CN), Ruijin Hospital (CN), Zhengzhou University (CN), Affiliated Hospital of Nantong University (CN), First Affiliated Hospital of Xiamen University (CN), First People's Hospital of Yunnan Province (CN), Second Affiliated Hospital of Dalian Medical University (CN), Nanfang Hospital (CN), Hunan Cancer Hospital (CN), Shandong Provincial Hospital (CN), Peking University People's Hospital (CN), First Hospital of Jilin University (CN), Henan Provincial People's Hospital (CN), Institut Français de la Vigne et du Vin (FR), Fujian Provincial Hospital (CN), Henan Cancer Hospital (CN), Shanghai Institute of Hematology (CN), Chongqing Cancer Hospital (CN), Hainan Medical College Hospital (CN), Tongji Hospital (CN), Union Hospital (CN), First Affiliated Hospital of Nanchang University (CN), Huazhong University of Science and Technology (CN), Southern Medical University (CN), Nanjing Medical University (CN)
National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Shanghai Hospital Development Center
Openalex Percentile: Top 45%
Lymphoma Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.