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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-11-3442.

Submitted November 14, 2002
Accepted January 19, 2003
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
ERM0220, Hopital Saint Louis, Paris, France
Service d'Anatomie Pathologique, Hopital Paul Brousse, Villejuif, France
Service de Medecine A, Hopital Brasbois, Nancy, France
Service d'Hematologie, Centre Leon Berard, Lyon, France
Service d'Anatomie Pathologique, Hopital Lyon Sud, Pierre Benite, France
Service d'Hematologie, Clinique Mont Godine, Yvoir, Belgium
Service d'Hematologie, Hopital Dr Schaffner, Lens, France
Service d'Hematologie, Centre Henry BequerelBerard, Rouen, France
Service d'Hematologie, Institut Paoli Calmette, Marseille, France
Service d'Hematologie, Hopital Henri Mondor, Creteil, France
Departement de Pathologie, Hopital Henri Mondor, Creteil, France
Service d'Hematologie, Hopital Lyon Sud, Pierre Benite, France
* Corresponding author; email: nicolas.mounier{at}sls.ap-hop-paris.fr.
In DLBCL, the combination of rituximab and CHOP (R-CHOP) has been proved more beneficial than CHOP alone for the treatment of elderly patients. Bcl-2 protein expression has been associated with poor prognosis in DLBCL patients. To establish, in vivo, whether or not rituximab reduces bcl-2 associated treatment failure, we studied bcl-2 expression and clinical outcome in patients included in the Groupe d'Etude des Lymphomes de l'Adulte (GELA) LNH-98-5 trial. Patients aged between 60 and 80 years 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-positive patients and 99 (34%) bcl-2-negative patients. The response rates for R-CHOP and CHOP were respectively 78 and 60% (P=0.01) in bcl-2-positive patients and 76 and 73% (P=0.7) in bcl-2-negative patients. At a median of 2 years' follow-up, R-CHOP was significantly associated with a better overall survival than CHOP in bcl-2-positive patients (67 ± 9% vs 48 ± 11%, P=0.004) but not in bcl-2-negative patients (72 ± 12% vs 67 ± 14%, P=0.6). In addition, R-CHOP was associated with significantly better event-free-survival than CHOP in bcl-2-positive patients (58 ± 10% vs 32 ± 10%, p<0.001) but not in bcl-2-negative patients (60 ± 13% vs 40 ± 15%, P=0.13). Multivariate analysis confirmed the significant benefit for survival and event-free-survival of R-CHOP in bcl-2 positive patients. These results suggest that rituximab is able to prevent chemotherapy failure in bcl-2 positive patients.

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S. Camilleri-Broet, E. Criniere, P. Broet, V. Delwail, K. Mokhtari, A. Moreau, M. Kujas, M. Raphael, W. Iraqi, C. Sautes-Fridman, et al.
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K. Leroy, J.-P. Jais, C. Haioun, D. Rickman, A. de Reynies, T. Molina, B. Coiffier, F. Berger, C. Gisselbrecht, J. Briere, et al.
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L. D. Kaplan, J. Y. Lee, R. F. Ambinder, J. A. Sparano, E. Cesarman, A. Chadburn, A. M. Levine, and D. T. Scadden
Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010
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C. Hoffmann, M. Tiemann, C. Schrader, D. Janssen, E. Wolf, M. Vierbuchen, R. Parwaresch, K. Ernestus, A. Plettenberg, A. Stoehr, et al.
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M. I. Vega, A. R. Jazirehi, S. Huerta-Yepez, and B. Bonavida
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J. S. Abramson and M. A. Shipp
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J. C. Reed and M. Pellecchia
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Y. Natkunam, I. S. Lossos, B. Taidi, S. Zhao, X. Lu, F. Ding, A. S. Hammer, T. Marafioti, G. E. Byrne Jr, S. Levy, et al.
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S. J. Horning
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A. P Levene, G. Singh, and C. Palmieri
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I. F. Khouri, R. M. Saliba, C. Hosing, G.-J. Okoroji, S. Acholonu, P. Anderlini, D. Couriel, M. De Lima, M. L. Donato, L. Fayad, et al.
Concurrent Administration of High-Dose Rituximab Before and After Autologous Stem-Cell Transplantation for Relapsed Aggressive B-Cell Non-Hodgkin's Lymphomas
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J. J. F. Muris, S. A. G. M. Cillessen, W. Vos, I. S. van Houdt, J. A. Kummer, J. H. J. M. van Krieken, N. M. Jiwa, P. M. Jansen, H. C. Kluin-Nelemans, G. J. Ossenkoppele, et al.
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J. O. Armitage
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J. W. Sweetenham
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E. Paszkiewicz-Kozik, O. Mioduszewska, I. Federowicz, E. Kraszewska, E. Kulczycka, K. Domanska-Czyz, B. Ostrowska, J. Romejko-Jarosinska, M. Osowiecki, and J. A. Walewski
Predictive Value of Bcl-2 and Bcl-6 Protein Expression in Diffuse Large B-Cell Lymphoma Patients from a Single Institution.
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G. Cartron, H. Watier, J. Golay, and P. Solal-Celigny
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B. Coiffier, G. Salles, M. Pfreundschuh, and M. Loeffler
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J. W. Friedberg
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M. Voulgarelis, S. Giannouli, D. Anagnostou, and A. G. Tzioufas
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M. Ghielmini, S.-F. H. Schmitz, S. B. Cogliatti, G. Pichert, J. Hummerjohann, U. Waltzer, M. F. Fey, D. C. Betticher, G. Martinelli, F. Peccatori, et al.
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F. Grange, T. Petrella, M. Beylot-Barry, P. Joly, M. D'Incan, M. Delaunay, L. Machet, M.-F. Avril, S. Dalac, P. Bernard, et al.
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J. A. Sparano, S. Lee, M. G. Chen, T. Nazeer, A. Einzig, R. F. Ambinder, D. H. Henry, J. Manalo, T. Li, and J. H. Von Roenn
Phase II Trial of Infusional Cyclophosphamide, Doxorubicin, and Etoposide in Patients With HIV-Associated Non-Hodgkin's Lymphoma: An Eastern Cooperative Oncology Group Trial (E1494)
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T. Decker, M. Oelsner, R. J. Kreitman, G. Salvatore, Q.-c. Wang, I. Pastan, C. Peschel, and T. Licht
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P. A. Volberding, K. R. Baker, and A. M. Levine
Human Immunodeficiency Virus Hematology
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