MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab

Anamarija M. Perry; Yuridia Alvarado-Bernal; Javier A. Laurini; Lynette M. Smith; Graham W. Slack; King L. Tan; Laurie H. Sehn; Kai Fu; Patricia Aoun; Timothy C. Greiner; Wing C. Chan; Philip J. Bierman; Robert G. Bociek; James O. Armitage; Julie M. Vose; Randy D. Gascoyne; Dennis D. Weisenburger

doi:10.1111/bjh.12763

MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab

Anamarija M. Perry, Yuridia Alvarado-Bernal, Javier A. Laurini, Lynette M. Smith, Graham W. Slack, King L. Tan, Laurie H. Sehn, Kai Fu, Patricia Aoun, Timothy C. Greiner, Wing C. Chan, Philip J. Bierman, Robert G. Bociek, James O. Armitage, Julie M. Vose, Randy D. Gascoyne, Dennis D. Weisenburger

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153 Scopus citations

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and "double-hit" DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or CHOP-like regimens. The results were validated on an independent cohort of 205 DLBCL patients. Patients with low expression of BCL2 (≤30%) and MYC (≤50%) had the best prognosis, whereas those with high BCL2 (>30%) and MYC (>50%) had the worst outcome. In multivariate analysis, the combination of the BCL2 and MYC was an independent predictor of overall survival (OS) and event-free survival (EFS) (P = 0·015 and P = 0·005, respectively). The risk of death was nine times greater for patients with high BCL2 and MYC compared to those with low expression. High BCL2 and MYC was a strong predictor of poor OS (P < 0·001) and EFS (P = 0·0017) in patients with the germinal centre B-cell (GCB) type, but not in the non-GCB type. In DLBCL, high co-expression of MYC and BCL2 was an independent predictor of poor survival, and could be used to stratify patients for risk-adapted therapies.

Original language	English (US)
Pages (from-to)	382-391
Number of pages	10
Journal	British Journal of Haematology
Volume	165
Issue number	3
DOIs	https://doi.org/10.1111/bjh.12763
State	Published - May 2014
Externally published	Yes

Keywords

Aggressive lymphoma
BCL2
Diffuse large B-cell lymphoma
Double-hit lymphoma
MYC

ASJC Scopus subject areas

Hematology

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10.1111/bjh.12763

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Perry, A. M., Alvarado-Bernal, Y., Laurini, J. A., Smith, L. M., Slack, G. W., Tan, K. L., Sehn, L. H., Fu, K., Aoun, P., Greiner, T. C., Chan, W. C., Bierman, P. J., Bociek, R. G., Armitage, J. O., Vose, J. M., Gascoyne, R. D., & Weisenburger, D. D. (2014). MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab. British Journal of Haematology, 165(3), 382-391. https://doi.org/10.1111/bjh.12763

Perry, AM, Alvarado-Bernal, Y, Laurini, JA, Smith, LM, Slack, GW, Tan, KL, Sehn, LH, Fu, K, Aoun, P, Greiner, TC, Chan, WC, Bierman, PJ, Bociek, RG, Armitage, JO, Vose, JM, Gascoyne, RD & Weisenburger, DD 2014, 'MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab', British Journal of Haematology, vol. 165, no. 3, pp. 382-391. https://doi.org/10.1111/bjh.12763

@article{61ee4416f89247279140d3c225404769,

title = "MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab",

abstract = "Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and {"}double-hit{"} DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or CHOP-like regimens. The results were validated on an independent cohort of 205 DLBCL patients. Patients with low expression of BCL2 (≤30%) and MYC (≤50%) had the best prognosis, whereas those with high BCL2 (>30%) and MYC (>50%) had the worst outcome. In multivariate analysis, the combination of the BCL2 and MYC was an independent predictor of overall survival (OS) and event-free survival (EFS) (P = 0·015 and P = 0·005, respectively). The risk of death was nine times greater for patients with high BCL2 and MYC compared to those with low expression. High BCL2 and MYC was a strong predictor of poor OS (P < 0·001) and EFS (P = 0·0017) in patients with the germinal centre B-cell (GCB) type, but not in the non-GCB type. In DLBCL, high co-expression of MYC and BCL2 was an independent predictor of poor survival, and could be used to stratify patients for risk-adapted therapies.",

keywords = "Aggressive lymphoma, BCL2, Diffuse large B-cell lymphoma, Double-hit lymphoma, MYC",

author = "Perry, {Anamarija M.} and Yuridia Alvarado-Bernal and Laurini, {Javier A.} and Smith, {Lynette M.} and Slack, {Graham W.} and Tan, {King L.} and Sehn, {Laurie H.} and Kai Fu and Patricia Aoun and Greiner, {Timothy C.} and Chan, {Wing C.} and Bierman, {Philip J.} and Bociek, {Robert G.} and Armitage, {James O.} and Vose, {Julie M.} and Gascoyne, {Randy D.} and Weisenburger, {Dennis D.}",

year = "2014",

month = may,

doi = "10.1111/bjh.12763",

language = "English (US)",

volume = "165",

pages = "382--391",

journal = "British Journal of Haematology",

issn = "0007-1048",

publisher = "Wiley-Blackwell",

number = "3",

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TY - JOUR

T1 - MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab

AU - Perry, Anamarija M.

AU - Alvarado-Bernal, Yuridia

AU - Laurini, Javier A.

AU - Smith, Lynette M.

AU - Slack, Graham W.

AU - Tan, King L.

AU - Sehn, Laurie H.

AU - Fu, Kai

AU - Aoun, Patricia

AU - Greiner, Timothy C.

AU - Chan, Wing C.

AU - Bierman, Philip J.

AU - Bociek, Robert G.

AU - Armitage, James O.

AU - Vose, Julie M.

AU - Gascoyne, Randy D.

AU - Weisenburger, Dennis D.

PY - 2014/5

Y1 - 2014/5

N2 - Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and "double-hit" DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or CHOP-like regimens. The results were validated on an independent cohort of 205 DLBCL patients. Patients with low expression of BCL2 (≤30%) and MYC (≤50%) had the best prognosis, whereas those with high BCL2 (>30%) and MYC (>50%) had the worst outcome. In multivariate analysis, the combination of the BCL2 and MYC was an independent predictor of overall survival (OS) and event-free survival (EFS) (P = 0·015 and P = 0·005, respectively). The risk of death was nine times greater for patients with high BCL2 and MYC compared to those with low expression. High BCL2 and MYC was a strong predictor of poor OS (P < 0·001) and EFS (P = 0·0017) in patients with the germinal centre B-cell (GCB) type, but not in the non-GCB type. In DLBCL, high co-expression of MYC and BCL2 was an independent predictor of poor survival, and could be used to stratify patients for risk-adapted therapies.

AB - Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and "double-hit" DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or CHOP-like regimens. The results were validated on an independent cohort of 205 DLBCL patients. Patients with low expression of BCL2 (≤30%) and MYC (≤50%) had the best prognosis, whereas those with high BCL2 (>30%) and MYC (>50%) had the worst outcome. In multivariate analysis, the combination of the BCL2 and MYC was an independent predictor of overall survival (OS) and event-free survival (EFS) (P = 0·015 and P = 0·005, respectively). The risk of death was nine times greater for patients with high BCL2 and MYC compared to those with low expression. High BCL2 and MYC was a strong predictor of poor OS (P < 0·001) and EFS (P = 0·0017) in patients with the germinal centre B-cell (GCB) type, but not in the non-GCB type. In DLBCL, high co-expression of MYC and BCL2 was an independent predictor of poor survival, and could be used to stratify patients for risk-adapted therapies.

KW - Aggressive lymphoma

KW - BCL2

KW - Diffuse large B-cell lymphoma

KW - Double-hit lymphoma

KW - MYC

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DO - 10.1111/bjh.12763

M3 - Article

C2 - 24506200

AN - SCOPUS:84898462636

SN - 0007-1048

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SP - 382

EP - 391

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 3

ER -

MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab

Abstract

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