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<p>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. <i>EZH2</i> mutation occurred more frequently in DHL/THL, while <i>TNFRSF14</i> mutation exhibited greater prevalence in THL. The EZB genotype was predominantly observed in DHL/THL patients, and those with <i>TP53</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月9日

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  • 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

摘要

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.