Negative impact of concurrent overexpression of MYC and BCL2 in patients with advanced diffuse large B-cell lymphoma treated with dose-intensified immunochemotherapy

被引：13

作者：

Takahashi, Hiromichi ^{[1
,2
]}

Miura, Katsuhiro ^{[1
]}

Nakagawa, Masaru ^{[1
]}

Sugitani, Masahiko ^{[3
]}

Amano, Yusuke ^{[3
]}

Kurita, Daisuke ^{[1
]}

Sakagami, Masashi ^{[1
]}

Ohtake, Shimon ^{[1
]}

Uchino, Yoshihito ^{[1
]}

Kodaira, Hitomi ^{[1
]}

Iriyama, Noriyoshi ^{[1
]}

Kobayashi, Sumiko ^{[1
]}

Hojo, Atsuko ^{[1
]}

Kobayashi, Yujin ^{[1
]}

Hirabayashi, Yukio ^{[1
]}

Kusuda, Machiko ^{[1
]}

Hatta, Yoshihiro ^{[1
]}

Nakayama, Tomohiro ^{[2
]}

Takei, Masami ^{[1
]}

机构：

[1] Nihon Univ, Div Hematol & Rheumatol, Dept Med, Sch Med, 30-1 Oyaguchikamicho, Tokyo 1738610, Japan

[2] Nihon Univ, Div Lab Med, Dept Pathol Microbiol, Sch Med, Tokyo, Japan

[3] Nihon Univ, Sch Med, Dept Pathol, Tokyo, Japan

来源：

LEUKEMIA & LYMPHOMA | 2016年 / 57卷 / 12期

关键词：

BCL2; diffuse large B-cell lymphoma; double-expressor lymphoma; high-dose chemotherapy; MYC; RITUXIMAB PLUS CYCLOPHOSPHAMIDE; NON-HODGKINS-LYMPHOMAS; DOUBLE-HIT LYMPHOMA; RESPONSE CRITERIA; CHOP; CONSOLIDATION; CHEMOTHERAPY; EXPRESSION; TRANSPLANTATION; ABNORMALITIES;

D O I：

10.3109/10428194.2016.1167205

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Co-expression of MYC and BCL2 proteins in diffuse large B-cell lymphoma (DLBCL), or 'double-expressor lymphoma' (DEL), results in poor patient prognosis, but the significance of DEL when aggressive treatments are applied remains uncertain. We performed a retrospective analysis of 40 patients with de novo DLBCL, who were categorized as being at high/high-intermediate risk according to the age-adjusted International Prognostic Index. Patients underwent an R-Double CHOP regimen, a dose-intensified immunochemotherapy with or without consolidative high-dose chemotherapy followed by autologous stem cell transplantation. According to immunohistochemical analysis, 10 (25%) patients were categorized as having DEL, showing positivity for MYC (>= 40%) and BCL2 (>= 50%). The 3 year progression-free survival and overall survival of the DEL group were significantly worse compared with those of the non-DEL group (30% vs. 63%, p=0.019 and 40% vs. 82%, p=0.006, respectively). These results suggest that advanced DEL may need discrete treatment strategies.

引用

页码：2784 / 2790

页数：7

共 28 条

[1] Double-hit B-cell lymphomas [J].

Aukema, Sietse M. ;

Siebert, Reiner ;

Schuuring, Ed ;

van Imhoff, Gustaaf W. ;

Kluin-Nelemans, Hanneke C. ;

Boerma, Evert-Jan ;

Kluin, Philip M. .

BLOOD, 2011, 117 (08) :2319-2331

[2] Isolated MYC cytogenetic abnormalities in diffuse large B-cell lymphoma do not predict an adverse clinical outcome [J].

Caponetti, Gabriel C. ;

Dave, Bhavana J. ;

Perry, Anamarija M. ;

Smith, Lynette M. ;

Jain, Smrati ;

Meyer, Paul N. ;

Bast, Martin ;

Bierman, Philip J. ;

Bociek, Robert G. ;

Vose, Julie M. ;

Armitage, James O. ;

Aoun, Patricia ;

Fu, Kai ;

Greiner, Timothy C. ;

Chan, Wing C. ;

Sanger, Warren G. ;

Weisenburger, Dennis D. .

LEUKEMIA & LYMPHOMA, 2015, 56 (11) :3082-3089

[3] Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas [J].

Cheson, BD ;

Horning, SJ ;

Coiffier, B ;

Shipp, MA ;

Fisher, RI ;

Connors, JM ;

Lister, TA ;

Vose, J ;

Grillo-López, A ;

Hagenbeek, A ;

Cabanillas, F ;

Klippensten, D ;

Hiddemann, W ;

Castellino, R ;

Harris, NL ;

Armitage, JO ;

Carter, W ;

Hoppe, R ;

Canellos, GP .

JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (04) :1244-1253

[4] Revised response criteria for malignant lymphoma [J].

Cheson, Bruce D. ;

Pfistner, Beate ;

Juweid, Malik E. ;

Gascoyne, Randy D. ;

Specht, Lena ;

Horning, Sandra J. ;

Coiffier, Bertrand ;

Fisher, Richard I. ;

Hagenbeek, Anton ;

Zucca, Emanuele ;

Rosen, Steven T. ;

Stroobants, Sigrid ;

Lister, T. Andrew ;

Hoppe, Richard T. ;

Dreyling, Martin ;

Tobinai, Kensei ;

Vose, Julie M. ;

Connors, Joseph M. ;

Federico, Massimo ;

Diehl, Volker .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (05) :579-586

[5]

Dunleavy K, 2014, BLOOD, V124, P395

[6] Immunohistochemical Double-Hit Score Is a Strong Predictor of Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone [J].

Green, Tina Marie ;

Young, Ken H. ;

Visco, Carlo ;

Xu-Monette, Zijun Y. ;

Orazi, Attilio ;

Go, Ronald S. ;

Nielsen, Ole ;

Gadeberg, Ole V. ;

Mourits-Andersen, Torben ;

Frederiksen, Mikael ;

Pedersen, Lars Moller ;

Moller, Michael Boe .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (28) :3460-3467

[7] Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray [J].

Hans, CP ;

Weisenburger, DD ;

Greiner, TC ;

Gascoyne, RD ;

Delabie, J ;

Ott, G ;

Müller-Hermelink, HK ;

Campo, E ;

Braziel, RM ;

Jaffe, ES ;

Pan, ZG ;

Farinha, P ;

Smith, LM ;

Falini, B ;

Banham, AH ;

Rosenwald, A ;

Staudt, LM ;

Connors, JM ;

Armitage, JO ;

Chan, WC .

BLOOD, 2004, 103 (01) :275-282

[8] MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma [J].

Horn, Heike ;

Ziepert, Marita ;

Becher, Claudia ;

Barth, Thomas F. E. ;

Bernd, Heinz-Wolfram ;

Feller, Alfred C. ;

Klapper, Wolfram ;

Hummel, Michael ;

Stein, Harald ;

Hansmann, Martin-Leo ;

Schmelter, Christopher ;

Moeller, Peter ;

Cogliatti, Sergio ;

Pfreundschuh, Michael ;

Schmitz, Norbert ;

Truemper, Lorenz ;

Siebert, Reiner ;

Loeffler, Markus ;

Rosenwald, Andreas ;

Ott, German .

BLOOD, 2013, 121 (12) :2253-2263

[9] MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program [J].

Hu, Shimin ;

Xu-Monette, Zijun Y. ;

Tzankov, Alexander ;

Green, Tina ;

Wu, Lin ;

Balasubramanyam, Aarthi ;

Liu, Wei-min ;

Visco, Carlo ;

Li, Yong ;

Miranda, Roberto N. ;

Montes-Moreno, Santiago ;

Dybkaer, Karen ;

Chiu, April ;

Orazi, Attilio ;

Zu, Youli ;

Bhagat, Govind ;

Richards, Kristy L. ;

Hsi, Eric D. ;

Choi, William W. L. ;

Zhao, Xiaoying ;

van Krieken, J. Han ;

Huang, Qin ;

Huh, Jooryung ;

Ai, Weiyun ;

Ponzoni, Maurilio ;

Ferreri, Andres J. M. ;

Zhou, Fan ;

Slack, Graham W. ;

Gascoyne, Randy D. ;

Tu, Meifeng ;

Variakojis, Daina ;

Chen, Weina ;

Go, Ronald S. ;

Piris, Miguel A. ;

Moller, Michael B. ;

Medeiros, L. Jeffrey ;

Young, Ken H. .

BLOOD, 2013, 121 (20) :4021-4031

[10] Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone [J].

Johnson, Nathalie A. ;

Slack, Graham W. ;

Savage, Kerry J. ;

Connors, Joseph M. ;

Ben-Neriah, Susana ;

Rogic, Sanja ;

Scott, David W. ;

Tan, King L. ;

Steidl, Christian ;

Sehn, Laurie H. ;

Chan, Wing C. ;

Iqbal, Javeed ;

Meyer, Paul N. ;

Lenz, Georg ;

Wright, George ;

Rimsza, Lisa M. ;

Valentino, Carlo ;

Brunhoeber, Patrick ;

Grogan, Thomas M. ;

Braziel, Rita M. ;

Cook, James R. ;

Tubbs, Raymond R. ;

Weisenburger, Dennis D. ;

Campo, Elias ;

Rosenwald, Andreas ;

Ott, German ;

Delabie, Jan ;

Holcroft, Christina ;

Jaffe, Elaine S. ;

Staudt, Louis M. ;

Gascoyne, Randy D. .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (28) :3452-3459

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