SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-11-3442. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3442v1 101/11/4279    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mounier, N. Articles by Coiffier, B. Search for Related Content PubMed PubMed Citation Articles by Mounier, N. Articles by Coiffier, B. Related Collections Neoplasia Apoptosis Oncogenes and Tumor Suppressors Immunotherapy Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4279-4284 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Rituximab plus CHOP (R-CHOP) overcomes bcl-2—associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL) Nicolas Mounier, Josette Briere, Christian Gisselbrecht, Jean-Francois Emile, Pierre Lederlin, Catherine Sebban, Francoise Berger, Andre Bosly, Pierre Morel, Herve Tilly, Reda Bouabdallah, Felix Reyes, Philippe Gaulard, and Bertrand Coiffier From the Service d'Onco-Hématologie, INSERM ERM0220-Hôpital Saint Louis, AP-HP, Paris, France; Service d'Anatomie Pathologique, Hôpital Paul Brousse, AP-HP, Villejuif, France; Service de Médecine A, Hôpital Brasbois, Vandoeuvre les Nancy, France; Service d'Hématologie, Centre Léon Bérard, Pierre Bénite, France; Service d'Anatomie Pathologique, Centre Hospitalier Lyon Sud, Pierre Bénite, France; Service d'Hématologie, Cliniques Universitaires de Mont Godine, Yvoir, Belgium; Service d'Hématologie, Hôpital du Docteur Schaffner, Lens, France; Service d'Hématologie, Centre Henri Becquerel, Rouen, France; Service d'Hématologie, Institut Paoli Calmette, Marseille, France; Service d'Hématologie, Hôpital Henri Mondor, AP-HP, Créteil, France; Département de Pathologie, EA2348-Hôpital Henri Mondor, AP-HP, Créteil, France; and Service d'Hématologie, Centre Hospitalier Lyon Sud, Lyon, France, for the Groupe d'Etude des Lymphomes de l'Adulte (GELA). In diffuse large B-cell lymphoma (DLBCL), the combination of rituximab and CHOP (cyclophosphamide, doxorubicine, vincristine, prednisone; R-CHOP) has been shown to be more effective than CHOP for the treatment of elderly patients. Bcl-2 protein expression has been associated with poor prognosis in patients with DLBCL. To establish whether or not rituximab reduces bcl-2—associated treatment failure, we studied bcl-2 protein expression and clinical outcome in patients included in the Groupe d'Etude des Lymphomes de l'Adulte LNH-98-5 trial. Patients between 60 and 80 years of age were randomized to receive 8 cycles of either CHOP or R-CHOP every 3 weeks. Of the 399 patients included, 292 with histologically proven DLBCL had material available for bcl-2 study. Tumors were considered positive when at least 50% of tumor cells expressed bcl-2 protein. There were 193 (66%) bcl-2+ patients and 99 (34%) bcl-2– patients. The response rates for R-CHOP and CHOP were, respectively, 78% and 60% (P = .01) in bcl-2+ patients and 76% and 73% (P = .7) in bcl-2– patients. At a median of 2 years of follow-up, R-CHOP was significantly associated with a better overall survival than CHOP in bcl-2+ patients (67% ± 9% versus 48% ± 11%, P = .004). In bcl-2– patients there was no statistically significant difference (72% ± 12% versus 67% ± 14%, P = .6). In addition, R-CHOP was associated with significantly better event-free survival than CHOP in bcl-2+ patients (58% ± 10% versus 32% ± 10%, P < .001) but not in bcl-2– patients (60% ± 13% versus 40% ± 15%, P = .13). Multivariate analysis confirmed the significant benefit for survival and event-free survival of R-CHOP in bcl-2+ patients. These results suggest that rituximab is able to prevent chemotherapy failure in patients with bcl-2 protein overexpression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Targeting CD20 Jane N. Winter Blood 2003 101: 4227. [Full Text] [PDF] This article has been cited by other articles: D. de Jong, A. Koster, A. Hagenbeek, J. Raemaekers, D. Veldhuizen, S. Heisterkamp, J. P. de Boer, and M. van Glabbeke Impact of the tumor microenvironment on prognosis in follicular lymphoma is dependent on specific treatment protocols Haematologica, January 1, 2009; 94(1): 70 - 77. [Abstract] [Full Text] [PDF] M. Ageberg, J. Linderoth, O. Linden, M. Jerkeman, and K. Drott Simvastatin Sensitizes Bcl-2-Negative DLBCL Cell Lines to CHOP: A Finding with Possible Clinical Implications for Treatment of Bcl-2-Negative DLBCL? Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 5044 - 5044. [Abstract] D. Ennishi, K. Takeuchi, M. Yokoyama, H. Asai, Y. Mishima, Y. Terui, S. Takahashi, H. Komatsu, K. Ikeda, M. Yamaguchi, et al. CD5 expression is potentially predictive of poor outcome among biomarkers in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy Ann. Onc., June 23, 2008; (2008) mdn392v1. [Abstract] [Full Text] [PDF] R. Malumbres, J. Chen, R. Tibshirani, N. A. Johnson, L. H. Sehn, Y. Natkunam, J. Briones, R. Advani, J. M. Connors, G. E. Byrne, et al. Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP Blood, June 15, 2008; 111(12): 5509 - 5514. [Abstract] [Full Text] [PDF] W. H. Wilson, K. Dunleavy, S. Pittaluga, U. Hegde, N. Grant, S. M. Steinberg, M. Raffeld, M. Gutierrez, B. A. Chabner, L. Staudt, et al. Phase II Study of Dose-Adjusted EPOCH and Rituximab in Untreated Diffuse Large B-Cell Lymphoma With Analysis of Germinal Center and Post-Germinal Center Biomarkers J. Clin. Oncol., June 1, 2008; 26(16): 2717 - 2724. [Abstract] [Full Text] [PDF] J. W. Friedberg Bak to death with chemotherapy Blood, June 1, 2008; 111(11): 5263 - 5264. [Full Text] [PDF] F. Jardin, P. Ruminy, J.-P. Kerckaert, F. Parmentier, J.-M. Picquenot, S. Quief, C. Villenet, G. Buchonnet, M. Tosi, T. Frebourg, et al. Detection of somatic quantitative genetic alterations by multiplex polymerase chain reaction for the prediction of outcome in diffuse large B-cell lymphomas Haematologica, April 1, 2008; 93(4): 543 - 550. [Abstract] [Full Text] [PDF] P. Morel, P. Gaulard, C. Gisselbrecht, C. Ferme, G. Salles, H. Tilly, J. Briere, M. C. Copin, P. Lederlin, O. Hermine, et al. Autologous stem-cell transplantation as consolidation therapy for diffuse large B-cell lymphoma patients with overexpression of bcl-2 protein. Results of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trial LNH98-B2 Ann. Onc., March 1, 2008; 19(3): 560 - 565. [Abstract] [Full Text] [PDF] G. A. Ulaner, P. M. Colletti, and P. S. Conti B-Cell Non-Hodgkin Lymphoma: PET/CT Evaluation after 90Y-Ibritumomab Tiuxetan Radioimmunotherapy--Initial Experience Radiology, March 1, 2008; 246(3): 895 - 902. [Abstract] [Full Text] [PDF] O. Determann, E. Hoster, G. Ott, H. Wolfram Bernd, C. Loddenkemper, M. Leo Hansmann, T. E. F. Barth, M. Unterhalt, W. Hiddemann, M. Dreyling, et al. Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group Blood, February 15, 2008; 111(4): 2385 - 2387. [Abstract] [Full Text] [PDF] Y. Natkunam, P. Farinha, E. D. Hsi, C. P. Hans, R. Tibshirani, L. H. Sehn, J. M. Connors, D. Gratzinger, M. Rosado, S. Zhao, et al. LMO2 Protein Expression Predicts Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With Anthracycline-Based Chemotherapy With and Without Rituximab J. Clin. Oncol., January 20, 2008; 26(3): 447 - 454. [Abstract] [Full Text] [PDF] D. Daniel, B. Yang, D. A. Lawrence, K. Totpal, I. Balter, W. P. Lee, A. Gogineni, M. J. Cole, S. F. Yee, S. Ross, et al. Cooperation of the proapoptotic receptor agonist rhApo2L/TRAIL with the CD20 antibody rituximab against non-Hodgkin lymphoma xenografts Blood, December 1, 2007; 110(12): 4037 - 4046. [Abstract] [Full Text] [PDF] S. Prakash and S. H Swerdlow Nodal aggressive B-cell lymphomas: a diagnostic approach J. Clin. Pathol., October 1, 2007; 60(10): 1076 - 1085. [Abstract] [Full Text] [PDF] F. Grange, M. Beylot-Barry, P. Courville, E. Maubec, M. Bagot, B. Vergier, P. Souteyrand, L. Machet, S. Dalac, E. Esteve, et al. Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type: Clinicopathologic Features and Prognostic Analysis in 60 Cases Arch Dermatol, September 1, 2007; 143(9): 1144 - 1150. [Abstract] [Full Text] [PDF] J. O. Armitage How I treat patients with diffuse large B-cell lymphoma Blood, July 1, 2007; 110(1): 29 - 36. [Full Text] [PDF] Y.-Y. Liu, C. Leboeuf, J.-Y. Shi, J.-M. Li, L. Wang, Y. Shen, J.-F. Garcia, Z.-X. Shen, Z. Chen, A. Janin, et al. Rituximab plus CHOP (R-CHOP) overcomes PRDM1-associated resistance to chemotherapy in patients with diffuse large B-cell lymphoma Blood, July 1, 2007; 110(1): 339 - 344. [Abstract] [Full Text] [PDF] J. Dupuis, P. Gaulard, F. Hemery, E. Itti, C. Gisselbrecht, A. Rahmouni, C. Copie-Bergman, J. Briere, T. E. Gnaoui, I. Gaillard, et al. Respective prognostic values of germinal center phenotype and early 18fluorodeoxyglucose-positron emission tomography scanning in previously untreated patients with diffuse large B-cell lymphoma Haematologica, June 1, 2007; 92(6): 778 - 783. [Abstract] [Full Text] [PDF] H. Nyman, M. Adde, M.-L. Karjalainen-Lindsberg, M. Taskinen, M. Berglund, R.-M. Amini, C. Blomqvist, G. Enblad, and S. Leppa Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy Blood, June 1, 2007; 109(11): 4930 - 4935. [Abstract] [Full Text] [PDF] H Veelken, S Vik Dannheim, J Schulte Moenting, U. Martens, J Finke, and A Schmitt-Graeff Immunophenotype as prognostic factor for diffuse large B-cell lymphoma in patients undergoing clinical risk-adapted therapy Ann. Onc., May 1, 2007; 18(5): 931 - 939. [Abstract] [Full Text] [PDF] D. de Jong, A. Rosenwald, M. Chhanabhai, P. Gaulard, W. Klapper, A. Lee, B. Sander, C. Thorns, E. Campo, T. Molina, et al. Immunohistochemical Prognostic Markers in Diffuse Large B-Cell Lymphoma: Validation of Tissue Microarray As a Prerequisite for Broad Clinical Applications--A Study From the Lunenburg Lymphoma Biomarker Consortium J. Clin. Oncol., March 1, 2007; 25(7): 805 - 812. [Abstract] [Full Text] [PDF] C. Bossard, K. Belhadj, F. Reyes, N. Martin-Garcia, F. Berger, J. A. Kummer, J. Briere, A.-C. Baglin, S. Cheze, J. Bosq, et al. Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials Blood, March 1, 2007; 109(5): 2183 - 2189. [Abstract] [Full Text] [PDF] L. H. Sehn, B. Berry, M. Chhanabhai, C. Fitzgerald, K. Gill, P. Hoskins, R. Klasa, K. J. Savage, T. Shenkier, J. Sutherland, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP Blood, March 1, 2007; 109(5): 1857 - 1861. [Abstract] [Full Text] [PDF] K. Dunleavy, R. E. Davis, O. Landgren, L. M. Staudt, and W. H. Wilson BCL-6 and rituximab in diffuse large B-cell lymphoma: where are we? Blood, January 15, 2007; 109(2): 843 - 844. [Full Text] [PDF] W. H. Wilson, K. Dunleavy, S. Pittaluga, N. Grant, M. Shovlin, S. Steinberg, M. Raffeld, L. Staudt, E. S. Jaffe, and J. Janik DA-EPOCH-R Is Highly Effective in Both BCL-6+ and BCL-6- Untreated De Novo Diffuse Large B-Cell Lymphoma (DLBCL): Study Update and Analysis of Survival Outcomes for Multiple Biomarkers. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 206 - 206. [Abstract] [Full Text] [PDF] P. Farinha, L. Sehn, B. Skinnider, J. M. Connors, and R. D. Gascoyne Addition of Rituximab (R) to CHOP Improves Survival in the Non-GCB Subtype of Diffuse Large B Cell Lymphoma (DLBCL). Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 816 - 816. [Abstract] [Full Text] [PDF] D. H. Kim, H. D. Jung, J. G. Kim, J.-J. Lee, D.-H. Yang, Y. H. Park, Y. R. Do, H. J. Shin, M. K. Kim, M. S. Hyun, et al. FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma Blood, October 15, 2006; 108(8): 2720 - 2725. [Abstract] [Full Text] [PDF] G. W. van Imhoff, E.-J. G. Boerma, B. van der Holt, E. Schuuring, L. F. Verdonck, H. C. Kluin-Nelemans, and P. M. Kluin Prognostic Impact of Germinal Center-Associated Proteins and Chromosomal Breakpoints in Poor-Risk Diffuse Large B-Cell Lymphoma J. Clin. Oncol., September 1, 2006; 24(25): 4135 - 4142. [Abstract] [Full Text] [PDF] C. Moskowitz Is it time to stop treating subsets of DLBCL with R-CHOP? Blood, June 1, 2006; 107(11): 4197 - 4198. [Full Text] [PDF] J. N. Winter, E. A. Weller, S. J. Horning, M. Krajewska, D. Variakojis, T. M. Habermann, R. I. Fisher, P. J. Kurtin, W. R. Macon, M. Chhanabhai, et al. Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study Blood, June 1, 2006; 107(11): 4207 - 4213. [Abstract] [Full Text] [PDF] A.-M. Tsimberidou, S. O'Brien, I. Khouri, F. J. Giles, H. M. Kantarjian, R. Champlin, S. Wen, K.-A. Do, S. C. Smith, S. Lerner, et al. Clinical Outcomes and Prognostic Factors in Patients With Richter's Syndrome Treated With Chemotherapy or Chemoimmunotherapy With or Without Stem-Cell Transplantation J. Clin. Oncol., May 20, 2006; 24(15): 2343 - 2351. [Abstract] [Full Text] [PDF] A. Tzankov, A. Gschwendtner, F. Augustin, M. Fiegl, E. C. Obermann, S. Dirnhofer, and P. Went Diffuse large B-cell lymphoma with overexpression of cyclin e substantiates poor standard treatment response and inferior outcome. Clin. Cancer Res., April 1, 2006; 12(7): 2125 - 2132. [Abstract] [Full Text] [PDF] I. S. Lossos and D. Morgensztern Prognostic Biomarkers in Diffuse Large B-Cell Lymphoma J. Clin. Oncol., February 20, 2006; 24(6): 995 - 1007. [Abstract] [Full Text] [PDF] J. Iqbal, V. T. Neppalli, G. Wright, B. J. Dave, D. E. Horsman, A. Rosenwald, J. Lynch, C. P. Hans, D. D. Weisenburger, T. C. Greiner, et al. BCL2 Expression Is a Prognostic Marker for the Activated B-Cell-Like Type of Diffuse Large B-Cell Lymphoma J. Clin. Oncol., February 20, 2006; 24(6): 961 - 968. [Abstract] [Full Text] [PDF] L. H. Sehn Optimal Use of Prognostic Factors in Non-Hodgkin Lymphoma Hematology, January 1, 2006; 2006(1): 295 - 302. [Abstract] [Full Text] [PDF] S. Camilleri-Broet, E. Criniere, P. Broet, V. Delwail, K. Mokhtari, A. Moreau, M. Kujas, M. Raphael, W. Iraqi, C. Sautes-Fridman, et al. A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases Blood, January 1, 2006; 107(1): 190 - 196. [Abstract] [Full Text] [PDF] K. Leroy, J.-P. Jais, C. Haioun, D. Rickman, A. de Reynies, T. Molina, B. Coiffier, F. Berger, C. Gisselbrecht, J. Briere, et al. Gene Expression Profile Associated with Survival in Patients with Diffuse Large B-Cell Lymphoma Treated by Chemotherapy and Rituximab. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 159 - 159. [Abstract]