TY - JOUR
T1 - Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL
AU - Savage, Kerry J.
AU - Slack, Graham W.
AU - Mottok, Anja
AU - Sehn, Laurie H.
AU - Villa, Diego
AU - Kansara, Roopesh
AU - Kridel, Robert
AU - Steidl, Christian
AU - Ennishi, Daisuke
AU - Tan, King L.
AU - Ben-Neriah, Susana
AU - Johnson, Nathalie A.
AU - Connors, Joseph M.
AU - Farinha, Pedro
AU - Scott, David W.
AU - Gascoyne, Randy D.
N1 - Funding Information:
This work was supported by the Canadian Institutes of Health Research, the British Columbia Cancer Foundation, and Grant No. 1023 from the Terry Fox Research Institute team.
Publisher Copyright:
© 2016 by The American Society of Hematology.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/5/5
Y1 - 2016/5/5
N2 - Dual expression of MYC and BCL2 by immunohistochemistry (IHC) is associated with poor outcome in diffuse large B-cell lymphoma (DLBCL). Dual translocation of MYC and BCL2, so-called "double-hit lymphoma," has been associated with a high risk of central nervous system (CNS) relapse; however, the impact of dual expression of MYC and BCL2 (dual expressers) on the risk of CNS relapse remains unknown. Pretreatment formalinfixed paraffin-embedded DLBCL biopsies derived from patients subsequently treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were assembled on tissue microarrays from 2 studies and were evaluated for expression of MYC and BCL2 by IHC. In addition, cell of origin was determined by IHC and the Lymph2Cx gene expression assay in a subset of patients. We identified 428 patients who met the inclusion criteria. By the recently described CNS risk score (CNS-International Prognostic Index [CNS-IPI]), 34% were low risk (0 to 1), 45% were intermediate risk (2 to 3), and 21% were high risk (4 or greater).With amedian follow-up of 6.8 years, the risk of CNS relapse was higher in dual expressers compared with non-dual expressers (2-year risk, 9.7%vs 2.2%;P=.001). Patients with activatedB-cell or non-germinal center B-cell type DLBCL also had an increased risk of CNS relapse. However, inmultivariate analysis, only dual expresser status and CNS-IPI were associated with CNS relapse. Dual expresser MYC+ BCL2+ DLBCL defines a group at high risk of CNS relapse, independent of CNS-IPI score and cell of origin. Dual expresser status may help to identify a high-risk group who should undergo CNS-directed evaluation and consideration of prophylactic strategies.
AB - Dual expression of MYC and BCL2 by immunohistochemistry (IHC) is associated with poor outcome in diffuse large B-cell lymphoma (DLBCL). Dual translocation of MYC and BCL2, so-called "double-hit lymphoma," has been associated with a high risk of central nervous system (CNS) relapse; however, the impact of dual expression of MYC and BCL2 (dual expressers) on the risk of CNS relapse remains unknown. Pretreatment formalinfixed paraffin-embedded DLBCL biopsies derived from patients subsequently treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were assembled on tissue microarrays from 2 studies and were evaluated for expression of MYC and BCL2 by IHC. In addition, cell of origin was determined by IHC and the Lymph2Cx gene expression assay in a subset of patients. We identified 428 patients who met the inclusion criteria. By the recently described CNS risk score (CNS-International Prognostic Index [CNS-IPI]), 34% were low risk (0 to 1), 45% were intermediate risk (2 to 3), and 21% were high risk (4 or greater).With amedian follow-up of 6.8 years, the risk of CNS relapse was higher in dual expressers compared with non-dual expressers (2-year risk, 9.7%vs 2.2%;P=.001). Patients with activatedB-cell or non-germinal center B-cell type DLBCL also had an increased risk of CNS relapse. However, inmultivariate analysis, only dual expresser status and CNS-IPI were associated with CNS relapse. Dual expresser MYC+ BCL2+ DLBCL defines a group at high risk of CNS relapse, independent of CNS-IPI score and cell of origin. Dual expresser status may help to identify a high-risk group who should undergo CNS-directed evaluation and consideration of prophylactic strategies.
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U2 - 10.1182/blood-2015-10-676700
DO - 10.1182/blood-2015-10-676700
M3 - Article
C2 - 26834242
AN - SCOPUS:84969143074
SN - 0006-4971
VL - 127
SP - 2182
EP - 2188
JO - Blood
JF - Blood
IS - 18
ER -