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CNS relapse in high-grade B-cell lymphoma with MYC and BCL2 rearrangements and dark-zone signature–expressing DLBCL
•CNS relapse rate in HGBCL-DH-BCL2 (6.8% at 2 years) is much lower than previously reported and is associated with clinical risk factors.•DZsig refines the cell-of-origin classification of DLBCL morphology tumors to inform CNS relapse risk stratification in GCB-DLBCL. [Display omitted] High-grade B-...
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Published in: | Blood 2024-10 |
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Main Authors: | , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | •CNS relapse rate in HGBCL-DH-BCL2 (6.8% at 2 years) is much lower than previously reported and is associated with clinical risk factors.•DZsig refines the cell-of-origin classification of DLBCL morphology tumors to inform CNS relapse risk stratification in GCB-DLBCL.
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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. |
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ISSN: | 0006-4971 1528-0020 1528-0020 |
DOI: | 10.1182/blood.2024025725 |