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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3725-3732.
Prepublished online as a Blood First Edition Paper on August 25, 2005; DOI 10.1182/blood-2005-01-0016.


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CLINICAL TRIALS AND OBSERVATIONS

Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group

Wolfgang Hiddemann, Michael Kneba, Martin Dreyling, Norbert Schmitz, Eva Lengfelder, Rudolf Schmits, Marcel Reiser, Bernd Metzner, Harriet Harder, Susanna Hegewisch-Becker, Thomas Fischer, Martin Kropff, Hans-Edgar Reis, Mathias Freund, Bernhard Wörmann, Roland Fuchs, Manfred Planker, Jörg Schimke, Hartmut Eimermacher, Lorenz Trümper, Ali Aldaoud, Reza Parwaresch, and Michael Unterhalt

From the Department of Internal Medicine III, University of Munich, Klinikum Großhadern; Department of Internal Medicine II, University Hospital Schleswig-Holstein, Campus Kiel; Department of Hematology and Oncology, Hospital St Georg, Hamburg; Department of Internal Medicine III, Klinikum Mannheim, University of Heidelberg; Department of Internal Medicine I, University of Homburg/Saar; Department of Internal Medicine I, University of Cologne; Department of Internal Medicine II, Oncology and Hematology, Klinikum Oldenburg; Department of Hematology, Oncology, and Tumor Immunology, Robert-Rössle-Klinik at the Helios Clinic Berlin-Buch, Charité, Campus Berlin-Buch; Department of Oncology, Klinikum Eppendorf, University of Hamburg; Department of Internal Medicine III, University of Mainz; Department of Internal Medicine A, University of Münster; Department of Hematology and Oncology, Kliniken Maria Hilf, Mönchengladbach; Department of Hematology and Oncology, University of Rostock; Department of Internal Medicine, Städtisches Klinikum Braunschweig; Department of Hematology and Oncology, St Antonius Hospital Eschweiler; Department of Hematology and Oncology, Städtische Krankenanstalten Krefeld; Praxis for Hematology and Oncology, Saarbrücken; Department of Hematology and Oncology, Katholisches Krankenhaus Hagen; Department of Hematology and Oncology, University of Göttingen; Praxis for Hematology and Oncology, Leipzig; and Department of Hemato-Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.

Phase 2 studies suggest that the monoclonal antibody rituximab may improve the prognosis of patients with follicular lymphoma (FL) when it is added to chemotherapy. In the current study, 428 patients with untreated, advanced-stage FL were randomly assigned for therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone (n = 205) or CHOP combined with rituximab (R-CHOP) (n = 223). R-CHOP reduced the relative risk for treatment failure by 60% and significantly prolonged the time to treatment failure (P < .001). In addition, a significantly higher overall response rate (96% vs 90%; P = .011) and a prolonged duration of remission (P = .001) were achieved. In spite of a relatively short observation time, these beneficial effects even translated to superior overall survival (P = .016), with 6 deaths in the R-CHOP group compared with 17 deaths in the CHOP group within the first 3 years. The predominant treatment-related adverse effect was myelosuppression. Severe granulocytopenia was more frequently observed after R-CHOP (63% vs 53%; P = .01). However, severe infections were rare and of similar frequency after R-CHOP and CHOP (5% and 7%). Hence, adding rituximab to CHOP significantly improves the outcome for patients with previously untreated advanced-stage FL and does not induce major adverse effects.


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Haematologica, August 1, 2007; 92(8): 1127 - 1130.
[Abstract] [Full Text] [PDF]


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A. Z.S. Rohatiner, L. Nadler, A. J. Davies, J. Apostolidis, D. Neuberg, J. Matthews, J. G. Gribben, P. M. Mauch, T. A. Lister, and A. S. Freedman
Myeloablative Therapy With Autologous Bone Marrow Transplantation for Follicular Lymphoma at the Time of Second or Subsequent Remission: Long-Term Follow-Up
J. Clin. Oncol., June 20, 2007; 25(18): 2554 - 2559.
[Abstract] [Full Text] [PDF]


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JCOHome page
S. Montoto, A. J. Davies, J. Matthews, M. Calaminici, A. J. Norton, J. Amess, S. Vinnicombe, R. Waters, A. Z.S. Rohatiner, and T. A. Lister
Risk and Clinical Implications of Transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
J. Clin. Oncol., June 10, 2007; 25(17): 2426 - 2433.
[Abstract] [Full Text] [PDF]


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M. H.J. van Oers
Rituximab maintenance therapy: a step forward in follicular lymphoma
Haematologica, June 1, 2007; 92(6): 826 - 833.
[Abstract] [Full Text] [PDF]


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J. G. Gribben
How I treat indolent lymphoma
Blood, June 1, 2007; 109(11): 4617 - 4626.
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M. Herold, A. Haas, S. Srock, S. Neser, K. H. Al-Ali, A. Neubauer, G. Dolken, R. Naumann, W. Knauf, M. Freund, et al.
Rituximab Added to First-Line Mitoxantrone, Chlorambucil, and Prednisolone Chemotherapy Followed by Interferon Maintenance Prolongs Survival in Patients With Advanced Follicular Lymphoma: An East German Study Group Hematology and Oncology Study
J. Clin. Oncol., May 20, 2007; 25(15): 1986 - 1992.
[Abstract] [Full Text] [PDF]


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JNCI J Natl Cancer InstHome page
H. Schulz, J. F. Bohlius, S. Trelle, N. Skoetz, M. Reiser, T. Kober, G. Schwarzer, M. Herold, M. Dreyling, M. Hallek, et al.
Immunochemotherapy With Rituximab and Overall Survival in Patients With Indolent or Mantle Cell Lymphoma: A Systematic Review and Meta-analysis
J Natl Cancer Inst, May 2, 2007; 99(9): 706 - 714.
[Abstract] [Full Text] [PDF]


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S. Vigouroux, M. Michallet, R. Porcher, M. Attal, L. Ades, M. Bernard, D. Blaise, R. Tabrizi, F. Garban, J.-P. Cassuto, et al.
Long-term outcomes after reduced-intensity conditioning allogeneic stem cell transplantation for low-grade lymphoma: a survey by the French Society of Bone Marrow Graft Transplantation and Cellular Therapy (SFGM-TC)
Haematologica, May 1, 2007; 92(5): 627 - 634.
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Ann OncolHome page
S Wohrer, M Troch, J Zwerina, G Schett, C Skrabs, A Gaiger, U Jaeger, C. Zielinski, and M Raderer
Influence of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone on serologic parameters and clinical course in lymphoma patients with autoimmune diseases
Ann. Onc., April 1, 2007; 18(4): 647 - 651.
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C. Nabhan
It Is Follicular... . So, Why CHOP?
J. Clin. Oncol., March 1, 2007; 25(7): 915 - 916.
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J. Immunol.Home page
A. J. Stel, B. ten Cate, S. Jacobs, J. W. Kok, D. C. J. Spierings, M. Dondorff, W. Helfrich, H. C. Kluin-Nelemans, L. F. M. H. de Leij, S. Withoff, et al.
Fas Receptor Clustering and Involvement of the Death Receptor Pathway in Rituximab-Mediated Apoptosis with Concomitant Sensitization of Lymphoma B Cells to Fas-Induced Apoptosis
J. Immunol., February 15, 2007; 178(4): 2287 - 2295.
[Abstract] [Full Text] [PDF]


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Ann OncolHome page
E Nitta, K Izutsu, T Sato, Y Ota, K Takeuchi, A Kamijo, K Takahashi, K Oshima, Y Kanda, S Chiba, et al.
A high incidence of late-onset neutropenia following rituximab-containing chemotherapy as a primary treatment of CD20-positive B-cell lymphoma: a single-institution study
Ann. Onc., February 1, 2007; 18(2): 364 - 369.
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Ann OncolHome page
C Nickenig, M Dreyling, E Hoster, W-D Ludwig, B Dorken, M Freund, C Huber, A Ganser, L Trumper, R Forstpointner, et al.
Initial chemotherapy with mitoxantrone, chlorambucil, prednisone impairs the collection of stem cells in patients with indolent lymphomas--results of a randomized comparison by the German Low-Grade Lymphoma Study Group
Ann. Onc., January 1, 2007; 18(1): 136 - 142.
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ASH Education BookHome page
G. A. Salles
Clinical Features, Prognosis and Treatment of Follicular Lymphoma
Hematology, January 1, 2007; 2007(1): 216 - 225.
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C. Bello and E. M. Sotomayor
Monoclonal Antibodies for B-Cell Lymphomas: Rituximab and Beyond
Hematology, January 1, 2007; 2007(1): 233 - 242.
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S. S. Neelapu and L. W. Kwak
Vaccine Therapy for B-Cell Lymphomas: Next-Generation Strategies
Hematology, January 1, 2007; 2007(1): 243 - 249.
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R. Forstpointner, M. Unterhalt, M. Dreyling, H.-P. Bock, R. Repp, H. Wandt, C. Pott, J. F. Seymour, B. Metzner, A. Hanel, et al.
Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG)
Blood, December 15, 2006; 108(13): 4003 - 4008.
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J. Vera, B. Savoldo, S. Vigouroux, E. Biagi, M. Pule, C. Rossig, J. Wu, H. E. Heslop, C. M. Rooney, M. K. Brenner, et al.
T lymphocytes redirected against the {kappa} light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells
Blood, December 1, 2006; 108(12): 3890 - 3897.
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M. H. J. van Oers, R. Klasa, R. E. Marcus, M. Wolf, E. Kimby, R. D. Gascoyne, A. Jack, M. van't Veer, A. Vranovsky, H. Holte, et al.
Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial
Blood, November 15, 2006; 108(10): 3295 - 3301.
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C. Sebban, N. Mounier, N. Brousse, C. Belanger, P. Brice, C. Haioun, H. Tilly, P. Feugier, R. Bouabdallah, C. Doyen, et al.
Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA)
Blood, October 15, 2006; 108(8): 2540 - 2544.
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M. F. Leahy, J. F. Seymour, R. J. Hicks, and J. H. Turner
Multicenter Phase II Clinical Study of Iodine-131-Rituximab Radioimmunotherapy in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
J. Clin. Oncol., September 20, 2006; 24(27): 4418 - 4425.
[Abstract] [Full Text] [PDF]


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Ann OncolHome page
F Cabanillas, I Liboy, O Pavia, and E Rivera
High incidence of non-neutropenic infections induced by rituximab plus fludarabine and associated with hypogammaglobulinemia: a frequently unrecognized and easily treatable complication.
Ann. Onc., September 1, 2006; 17(9): 1424 - 1427.
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O. W. Press, J. M. Unger, R. M. Braziel, D. G. Maloney, T. P. Miller, M. LeBlanc, and R. I. Fisher
Phase II Trial of CHOP Chemotherapy Followed by Tositumomab/Iodine I-131 Tositumomab for Previously Untreated Follicular Non-Hodgkin's Lymphoma: Five-Year Follow-Up of Southwest Oncology Group Protocol S9911
J. Clin. Oncol., September 1, 2006; 24(25): 4143 - 4149.
[Abstract] [Full Text] [PDF]


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D. Decaudin, P. de Cremoux, A. Vincent-Salomon, R. Dendale, and L. L.-L. Rouic
Ocular adnexal lymphoma: a review of clinicopathologic features and treatment options
Blood, September 1, 2006; 108(5): 1451 - 1460.
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C. Buske, E. Hoster, M. Dreyling, J. Hasford, M. Unterhalt, W. Hiddemann, and for the German Low Grade Lymphoma Study Group (GLS
The Follicular Lymphoma International Prognostic Index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to treatment outcome
Blood, September 1, 2006; 108(5): 1504 - 1508.
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Ann OncolHome page
A. K. Ganti, D. D. Weisenburger, L. M. Smith, C. P. Hans, R. G. Bociek, P. J. Bierman, J. M. Vose, and J. O. Armitage
Patients with grade 3 follicular lymphoma have prolonged relapse-free survival following anthracycline-based chemotherapy: the Nebraska Lymphoma Study Group Experience
Ann. Onc., June 1, 2006; 17(6): 920 - 927.
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K. Dunleavy, W. H. Wilson, and L. D. Kaplan
The case for rituximab in AIDS-related lymphoma.
Blood, April 1, 2006; 107(7): 3014 - 3015.
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L. H. Sehn
Optimal Use of Prognostic Factors in Non-Hodgkin Lymphoma
Hematology, January 1, 2006; 2006(1): 295 - 302.
[Abstract] [Full Text] [PDF]


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M. S. Czuczman
Controversies in Follicular Lymphoma: "Who, What, When, Where, and Why?" (Not Necessarily in That Order!)
Hematology, January 1, 2006; 2006(1): 303 - 310.
[Abstract] [Full Text] [PDF]



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