This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gisselbrecht, C. Articles by Reyes, F. Search for Related Content PubMed PubMed Citation Articles by Gisselbrecht, C. Articles by Reyes, F. Social Bookmarking                            What's this?

Shortened First-Line High-Dose Chemotherapy for Patients With Poor-Prognosis Aggressive Lymphoma

From the Institut d’Hématologie, GELA Hôpital Saint Louis; Service d’Anatomie Pathologique, Hôtel Dieu; Service d’Hématologie, Hôpital Pitié Salpétrière; Service d’Hématologie, Hôpital Necker, Paris; Departement d’Information Hospitalier, Hôpital Henri Mondor; Service d’Hématologie, Hôpital Henri Mondor, Créteil; Centre Hospitalier Universitaire de Lille, Lille; Service d’Hématologie et Medecine interne, Centre Hospitalier Universitaire Brabois, Vandoeuvre les Nancy; Centre Hospitalier Lyon Sud, Pierre Bénite; Centre Henri Becquerel, Rouen; Service d’Hématologie, Hôpital Beaujon, Clichy, France; and Centre Hospitalier Universitaire de Liège, Domaine Universitaire de Sart Tilman, Liège, Belgium.

Address reprint requests to Christian Gisselbrecht, MD, Institut d’Hématologie, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75475 Paris cedex 10, France; email: christian.gisselbrecht{at}sls.ap-hop-paris.fr

PURPOSE: Randomized trial LNH93-3 was conducted on patients who had poor-prognosis aggressive lymphoma and were younger than 60 years with two to three factors of the age-adjusted International Prognostic Index to evaluate the benefit of early high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT).

PATIENTS AND METHODS: Patients were randomized between doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) chemotherapy followed by sequential consolidation and an experimental shortened treatment consisting of three cycles with escalated doses of cyclophosphamide, epirubicin, vindesine, bleomycin, and prednisone and collection of peripheral-blood stem cells. On day 60, HDT was administered with 1,3-bis(2-chloroethyl)-1-nitrosourea, etoposide, cytarabine, and melphalan followed by ASCT.

RESULTS: Eligible patients (n = 370) with aggressive lymphoma were analyzed. For ACVBP (181 patients) and HDT (189 patients), respective complete remission rates were 64% and 63%. With a median follow-up of 60 months, 5-year overall survival and event-free survival for ACVBP and HDT were 60% ± 8% and 46% ± 8% (P = .007) and 52 ± 8% and 39 ± 8% (P = .01), respectively. Survival was independently affected by age greater than 40 years (P = .0003), T-cell phenotype (P = .009), bone marrow involvement (P = .003), and HDT treatment group (P = .04).

CONCLUSION: Early HDT with ASCT in high-risk patients was inferior to the ACVBP chemotherapy regimen. These results indicate that the received dose-intensity before HDT was too low when compared with ACVBP and HDT and was given too early.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				F. R. Loberiza Jr, A. J. Cannon, D. D. Weisenburger, J. M. Vose, M. J. Moehr, M. A. Bast, P. J. Bierman, R. G. Bociek, and J. O. Armitage Survival Disparities in Patients With Lymphoma According to Place of Residence and Treatment Provider: A Population-Based Study J. Clin. Oncol., November 10, 2009; 27(32): 5376 - 5382. [Abstract] [Full Text] [PDF]

				P. Reimer, T. Rudiger, E. Geissinger, F. Weissinger, C. Nerl, N. Schmitz, A. Engert, H. Einsele, H. K. Muller-Hermelink, and M. Wilhelm Autologous Stem-Cell Transplantation As First-Line Therapy in Peripheral T-Cell Lymphomas: Results of a Prospective Multicenter Study J. Clin. Oncol., January 1, 2009; 27(1): 106 - 113. [Abstract] [Full Text] [PDF]

				E. Jantunen, C. Canals, A. Rambaldi, G. Ossenkoppele, B. Allione, D. Blaise, E. Conde, H. Tilly, G. Cook, F. Clark, et al. Autologous stem cell transplantation in elderly patients (>=60 years) with diffuse large B-cell lymphoma: an analysis based on data in the European Blood and Marrow Transplantation registry Haematologica, December 1, 2008; 93(12): 1837 - 1842. [Abstract] [Full Text] [PDF]

				N. Mourad, N. Mounier, J. Briere, E. Raffoux, A. Delmer, A. Feller, C. J. L. M. Meijer, J.-F. Emile, R. Bouabdallah, A. Bosly, et al. Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials Blood, May 1, 2008; 111(9): 4463 - 4470. [Abstract] [Full Text] [PDF]

				A. R. Shustov and K. J. Savage Does High-Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation Have a Role in the Primary Treatment of Peripheral T-Cell Lymphomas? Hematology, January 1, 2008; 2008(1): 39 - 41. [Abstract] [Full Text] [PDF]

				S. M. Horwitz Novel Therapies and Role of Transplant in the Treatment of Peripheral T-Cell Lymphomas Hematology, January 1, 2008; 2008(1): 289 - 296. [Abstract] [Full Text] [PDF]

				N. Schmitz, P. Dreger, B. Glass, and A. Sureda Allogeneic transplantation in lymphoma: current status Haematologica, November 1, 2007; 92(11): 1533 - 1548. [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]

				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]

				J. Dupuis, J.-F. Emile, N. Mounier, C. Gisselbrecht, N. Martin-Garcia, T. Petrella, R. Bouabdallah, F. Berger, A. Delmer, B. Coiffier, et al. Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: a Groupe d'Etude des Lymphomes de l'Adulte (GELA) study Blood, December 15, 2006; 108(13): 4163 - 4169. [Abstract] [Full Text] [PDF]

				K. van Besien Autologous transplantation for follicular lymphoma? Not too soon! Blood, October 15, 2006; 108(8): 2496 - 2497. [Full Text] [PDF]

				D. Betticher, G Martinelli, J. Radford, M Kaufmann, M. Dyer, U Kaiser, W. Aulitzky, J Beck, A von Rohr, T Kovascovics, et al. Sequential high dose chemotherapy as initial treatment for aggressive sub-types of Non-Hodgkin Lymphoma: results of the international randomized phase III trial (MISTRAL) Ann. Onc., October 1, 2006; 17(10): 1546 - 1552. [Abstract] [Full Text] [PDF]

				D. A. Stewart, N. Bahlis, K. Valentine, A. Balogh, L. Savoie, D. G. Morris, A. Jones, C. Brown, and J. A. Russell Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma Blood, June 15, 2006; 107(12): 4623 - 4627. [Abstract] [Full Text] [PDF]

				B. Glass, M. Kloess, M. Bentz, G. Schlimok, W. E. Berdel, A. Feller, L. Trumper, M. Loeffler, M. Pfreundschuh, N. Schmitz, et al. Dose-escalated CHOP plus etoposide (MegaCHOEP) followed by repeated stem cell transplantation for primary treatment of aggressive high-risk non-Hodgkin lymphoma Blood, April 15, 2006; 107(8): 3058 - 3064. [Abstract] [Full Text] [PDF]

				C. Besson, D. Canioni, E. Lepage, S. Pol, P. Morel, P. Lederlin, A. Van Hoof, H. Tilly, P. Gaulard, B. Coiffier, et al. Characteristics and Outcome of Diffuse Large B-Cell Lymphoma in Hepatitis C Virus-Positive Patients in LNH 93 and LNH 98 Groupe d'Etude des Lymphomes de l'Adulte Programs J. Clin. Oncol., February 20, 2006; 24(6): 953 - 960. [Abstract] [Full Text] [PDF]

				A. Olivieri, G. Santini, C. Patti, T. Chisesi, C. De Souza, A. Rubagotti, S. Aversa, A. Billio, A. Porcellini, M. Candela, et al. Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG Ann. Onc., December 1, 2005; 16(12): 1941 - 1948. [Abstract] [Full Text] [PDF]

				S. A. Gregory and L. Trumper Chemotherapy dose intensity in non-Hodgkin's lymphoma: is dose intensity an emerging paradigm for better outcomes? Ann. Onc., September 1, 2005; 16(9): 1413 - 1424. [Abstract] [Full Text] [PDF]

				J. S. Abramson and M. A. Shipp Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach Blood, August 15, 2005; 106(4): 1164 - 1174. [Abstract] [Full Text] [PDF]

				G. W. van Imhoff, B. van der Holt, M. A. MacKenzie, M. B. van't Veer, P. W. Wijermans, G. J. Ossenkoppele, H. C. Schouten, P. Sonneveld, M. M.C. Steijaert, P. M. Kluin, et al. Impact of Three Courses of Intensified CHOP Prior to High-Dose Sequential Therapy Followed by Autologous Stem-Cell Transplantation As First-Line Treatment in Poor-Risk, Aggressive Non-Hodgkin's Lymphoma: Comparative Analysis of Dutch-Belgian Hemato-Oncology Cooperative Group Studies 27 and 40 J. Clin. Oncol., June 1, 2005; 23(16): 3793 - 3801. [Abstract] [Full Text] [PDF]

				N. Mounier, C. Gisselbrecht, J. Briere, C. Haioun, P. Feugier, F. Offner, C. Recher, A. Stamatoullas, F. Morschhauser, M. Macro, et al. All aggressive lymphoma subtypes do not share similar outcome after front-line autotransplantation: a matched-control analysis by the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Ann. Onc., December 1, 2004; 15(12): 1790 - 1797. [Abstract] [Full Text] [PDF]

				N. Mounier, C. Gisselbrecht, J. Briere, C. Haioun, P. Feugier, F. Offner, C. Recher, A. Stamatoullas, F. Morschhauser, M. Macro, et al. Prognostic Factors in Patients With Aggressive Non-Hodgkin's Lymphoma Treated by Front-Line Autotransplantation After Complete Remission: A Cohort Study by the Groupe d'Etude des Lymphomes de l'Adulte J. Clin. Oncol., July 15, 2004; 22(14): 2826 - 2834. [Abstract] [Full Text] [PDF]

				D. Aguiar Bujanda, U. Bohn Sarmiento, J. Aguiar Morales, J. Bolanos-Meade, Y. Herishanu, A. Zomas, A. Skandalis, and N. Milpied Intensive Therapy for Aggressive Lymphoma N. Engl. J. Med., July 1, 2004; 351(1): 98 - 100. [Full Text] [PDF]

				N. Milpied, E. Deconinck, F. Gaillard, V. Delwail, C. Foussard, C. Berthou, R. Gressin, V. Lucas, P. Colombat, J.-L. Harousseau, et al. Initial Treatment of Aggressive Lymphoma with High-Dose Chemotherapy and Autologous Stem-Cell Support N. Engl. J. Med., March 25, 2004; 350(13): 1287 - 1295. [Abstract] [Full Text] [PDF]

				M. Andre, N. Mounier, X. Leleu, A. Sonet, P. Brice, M. Henry-Amar, H. Tilly, B. Coiffier, A. Bosly, P. Morel, et al. Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients Blood, February 15, 2004; 103(4): 1222 - 1228. [Abstract] [Full Text] [PDF]

				M. Binn, A. Ruskone-Fourmestraux, E. Lepage, C. Haioun, A. Delmer, P. Aegerter, A. Lavergne, C. Guettier, and J.-C. Delchier Surgical resection plus chemotherapy versus chemotherapy alone: comparison of two strategies to treat diffuse large B-cell gastric lymphoma Ann. Onc., December 1, 2003; 14(12): 1751 - 1757. [Abstract] [Full Text] [PDF]

				B. Coiffier Increasing Chemotherapy Intensity in Aggressive Lymphomas: A Renewal? J. Clin. Oncol., July 1, 2003; 21(13): 2457 - 2459. [Full Text] [PDF]

				D. W. Blayney, M. L. LeBlanc, T. Grogan, E. R. Gaynor, R. A. Chapman, C. H. Spiridonidis, S. A. Taylor, S. I. Bearman, T. P. Miller, and R. I. Fisher Dose-Intense Chemotherapy Every 2 Weeks With Dose-Intense Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone May Improve Survival in Intermediate- and High-Grade Lymphoma: A Phase II Study of the Southwest Oncology Group (SWOG 9349) J. Clin. Oncol., July 1, 2003; 21(13): 2466 - 2473. [Abstract] [Full Text] [PDF]

				J.N. Munck Shorter is not Better J. Clin. Oncol., April 15, 2003; 21(8): 1648 - 1648. [Full Text] [PDF]

				R. Bouabdallah, N. Mounier, C. Guettier, T. Molina, V. Ribrag, C. Thieblemont, A. Sonet, A. Delmer, K. Belhadj, P. Gaulard, et al. T-Cell/Histiocyte-Rich Large B-Cell Lymphomas and Classical Diffuse Large B-Cell Lymphomas Have Similar Outcome After Chemotherapy: A Matched-Control Analysis J. Clin. Oncol., April 1, 2003; 21(7): 1271 - 1277. [Abstract] [Full Text] [PDF]

				K. Takeyama, M. Ogura, Y. Morishima, M. Kasai, Y. Kiyama, K. Ohnishi, H. Mitsuya, F. Kawano, Y. Masaki, T. Sasaki, et al. A Dose-finding Study of Glycosylated G-CSF (Lenograstim) Combined with CHOP Therapy for Stem Cell Mobilization in Patients with Non-Hodgkin's Lymphoma Jpn. J. Clin. Oncol., February 1, 2003; 33(2): 78 - 85. [Abstract] [Full Text] [PDF]

				R. I. Fisher Autologous Stem-Cell Transplantation as a Component of Initial Treatment for Poor-Risk Patients With Aggressive Non-Hodgkin's Lymphoma: Resolved Issues Versus Remaining Opportunity J. Clin. Oncol., November 15, 2002; 20(22): 4411 - 4412. [Full Text] [PDF]

				U. Kaiser, I. Uebelacker, U. Abel, J. Birkmann, L. Trumper, H. Schmalenberg, T. Karakas, B. Metzner, D. K. Hossfeld, H. G. Bischoff, et al. Randomized Study to Evaluate the Use of High-Dose Therapy as Part of Primary Treatment for "Aggressive" Lymphoma J. Clin. Oncol., November 15, 2002; 20(22): 4413 - 4419. [Abstract] [Full Text] [PDF]