Alduaij Waleed, Jiang Aixiang, Villa Diego, Collinge Brett, Ben-Neriah Susana, Boyle Merrill, Meissner Barbara, Hilton Laura K, Farinha Pedro, Slack Graham W, Craig Jeffrey W, Gerrie Alina S, Freeman Ciara L, Mungall Andrew J, Steidl Christian, Sehn Laurie H, Scott David W, Savage Kerry J
Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.
Division of Medical Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Blood. 2025 Feb 6;145(6):590-596. doi: 10.1182/blood.2024025725.
High-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2), or "double-hit lymphoma," has been associated with a high risk of central nervous system (CNS) relapse. However, historic estimates are impacted by selection bias. We report CNS relapse rates associated with HGBCL-DH-BCL2 from a population-based cohort with complete fluorescence in situ hybridization testing, as well as diffuse large B-cell lymphoma morphology (DLBCL) tumors expressing the dark-zone gene expression signature (DZsig), which was originally derived from HGBCL-DH-BCL2. The 2-year CNS relapse risk in HGBCL-DH-BCL2 was 6.8%. CNS relapses were early, predominantly leptomeningeal (73%), and co-occurred with systemic relapse (64%). High-risk CNS International Prognostic Index (CNS-IPI) and concordant bone marrow involvement were associated with an elevated CNS relapse risk in HGBCL-DH-BCL2. The "refined cell-of-origin" classification assigned 20% of DLBCL morphology tumors with germinal center B-cell-like phenotype (GCB-DLBCL) into a distinct subgroup based on DZsig expression (DZsig+). CNS relapse risk in DZsig+ (2 year: 6.4%) was independent of HGBCL-DH-BCL2 status and was further stratified by the CNS-IPI. CNS relapse in DZsig-negative GCB-DLBCL was rare (2-year risk, 1.4%; P = .04 vs DZsig+) and exclusively parenchymal. Altogether, the CNS relapse risk in HGBCL-DH-BCL2 is lower than previously reported, and DZsig refines risk stratification in GCB-DLBCL.
伴有MYC和BCL2重排的高级别B细胞淋巴瘤（HGBCL-DH-BCL2），即“双打击淋巴瘤”，与中枢神经系统（CNS）复发的高风险相关。然而，既往的估计受到选择偏倚的影响。我们报告了来自一个基于人群的队列中HGBCL-DH-BCL2相关的CNS复发率，该队列进行了完整的荧光原位杂交检测，以及表达暗区基因表达特征（DZsig）的弥漫性大B细胞淋巴瘤形态（DLBCL）肿瘤，DZsig最初源自HGBCL-DH-BCL2。HGBCL-DH-BCL2中2年CNS复发风险为6.8%。CNS复发较早，主要为软脑膜复发（73%），并与全身复发同时发生（64%）。高危CNS国际预后指数（CNS-IPI）和一致的骨髓受累与HGBCL-DH-BCL2中CNS复发风险升高相关。“精细细胞起源”分类根据DZsig表达（DZsig+）将20%具有生发中心B细胞样表型（GCB-DLBCL）的DLBCL形态肿瘤归为一个独特的亚组。DZsig+组（2年：6.4%）的CNS复发风险独立于HGBCL-DH-BCL2状态，并进一步根据CNS-IPI进行分层。DZsig阴性的GCB-DLBCL中CNS复发罕见（2年风险，1.4%；与DZsig+组相比，P = 0.04），且均为实质复发。总体而言，HGBCL-DH-BCL2中的CNS复发风险低于先前报道，且DZsig改善了GCB-DLBCL中的风险分层。
