CNS relapse in high-grade B-cell lymphoma with <i>MYC</i> and <i>BCL2</i> rearrangements and dark-zone signature–expressing DLBCL
Abstract
Abstract 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.
Article Details
Authors (18)
Waleed Alduaij
1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada
Aixiang Jiang
1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada
Diego Villa
8Division of Medical Oncology, BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, Canada
Brett Collinge
1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada
Susana Ben-Neriah
1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada
Merrill Boyle
1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada
Barbara Meissner
1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada
Laura K. Hilton
4Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada
Pedro Farinha
6BC Cancer, Vancouver, BC, Canada
Graham W. Slack
6BC Cancer, Vancouver, BC, Canada
Jeffrey W. Craig
Department of Pathology University of Virginia Medical Center Charlottesville Virginia USA
Alina S. Gerrie
21BC Cancer Centre for Lymphoid Cancer, University of British Columbia, Vancouver, BC, Canada
Ciara L. Freeman
7Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Andrew J. Mungall
5Canada’s Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada
Christian Steidl
5Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, Canada
Laurie H. Sehn
8Division of Medical Oncology, BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, Canada
David W. Scott
5Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, Canada
Kerry J. Savage
6BC Cancer, Vancouver, BC, Canada