Journal of Clinical Oncology, Vol 16, 3803-3809, Copyright © 1998 by American Society of Clinical Oncology

ARTICLES

Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma

IF Khouri, J Romaguera, H Kantarjian, JL Palmer, WC Pugh, M Korbling, F Hagemeister, B Samuels, A Rodriguez, S Giralt, A Younes, D Przepiorka, D Claxton, F Cabanillas and R Champlin
Department of Hematology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA. issafkhouri@mdanderson.org

PURPOSE: Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara- C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation. PATIENTS AND METHODS: Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants. RESULTS: Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = .007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP)-like regimen, untreated patients in the study had a 3- year EFS rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants. CONCLUSION: The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. S. Tam, R. Bassett, C. Ledesma, M. Korbling, A. Alousi, C. Hosing, P. Kebraei, R. Harrell, G. Rondon, S. A. Giralt, et al. Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma Blood, April 30, 2009; 113(18): 4144 - 4152. [Abstract] [Full Text] [PDF]

				A. Goy, S. H. Bernstein, B. S. Kahl, B. Djulbegovic, M. J. Robertson, S. de Vos, E. Epner, A. Krishnan, J. P. Leonard, S. Lonial, et al. Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study Ann. Onc., March 1, 2009; 20(3): 520 - 525. [Abstract] [Full Text] [PDF]

				J. R. Bertino Transfer of drug resistance genes into hematopoietic stem cells for marrow protection. Oncologist, October 1, 2008; 13(10): 1036 - 1042. [Full Text] [PDF]

				C. H. Geisler, A. Kolstad, A. Laurell, N. S. Andersen, L. B. Pedersen, M. Jerkeman, M. Eriksson, M. Nordstrom, E. Kimby, A. M. Boesen, et al. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group Blood, October 1, 2008; 112(7): 2687 - 2693. [Abstract] [Full Text] [PDF]

				D. L. Ornstein, C. B. Bifulco, D. T. Braddock, and J. G. Howe Histopathologic and Molecular Aspects of CD56+ Natural Killer/ T-Cell Lymphoma of the Testis International Journal of Surgical Pathology, July 1, 2008; 16(3): 291 - 300. [Abstract] [PDF]

				C. Hosing, R. M. Saliba, G.-J. Okoroji, U. Popat, D. Couriel, T. Ali, L. De Padua Silva, P. Kebriaei, A. Alousi, M. De Lima, et al. High-dose chemotherapy and autologous hematopoietic progenitor cell transplantation for non-Hodgkin's lymphoma in patients >65 years of age Ann. Onc., June 1, 2008; 19(6): 1166 - 1171. [Abstract] [Full Text] [PDF]

				A. Ferrer, F. Bosch, N. Villamor, M. Rozman, F. Graus, G. Gutierrez, S. Mercadal, E. Campo, C. Rozman, A. Lopez-Guillermo, et al. Central nervous system involvement in mantle cell lymphoma Ann. Onc., January 1, 2008; 19(1): 135 - 141. [Abstract] [Full Text] [PDF]

				B. S. Kahl New Therapeutic Strategies for Mantle Cell Lymphoma ASCO Educational Book, January 1, 2008; 2008(1): 392 - 397. [Abstract] [Full Text] [PDF]

				P. Dreger, M. Rieger, B. Seyfarth, M. Hensel, M. Kneba, A. D. Ho, N. Schmitz, and C. Pott Rituximab-augmented myeloablation for first-line autologous stem cell transplantation for mantle cell lymphoma: effects on molecular response and clinical outcome Haematologica, January 1, 2007; 92(1): 42 - 49. [Abstract] [Full Text] [PDF]

				R. I. Fisher, S. H. Bernstein, B. S. Kahl, B. Djulbegovic, M. J. Robertson, S. de Vos, E. Epner, A. Krishnan, J. P. Leonard, S. Lonial, et al. Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma J. Clin. Oncol., October 20, 2006; 24(30): 4867 - 4874. [Abstract] [Full Text] [PDF]

				L. E. Toner, R. Vrhovac, E. A. Smith, J. Gardner, M. Heaney, M. Gonen, J. Teruya-Feldstein, F. Sirotnak, and O. A. O'Connor The Schedule-Dependent Effects of the Novel Antifolate Pralatrexate and Gemcitabine Are Superior to Methotrexate and Cytarabine in Models of Human Non-Hodgkin's Lymphoma Clin. Cancer Res., February 1, 2006; 12(3): 924 - 932. [Abstract] [Full Text] [PDF]

				F. Ravandi and S. O'Brien Chronic Lymphoid Leukemias Other Than Chronic Lymphocytic Leukemia: Diagnosis and Treatment Mayo Clin. Proc., December 1, 2005; 80(12): 1660 - 1674. [Abstract] [PDF]

				J. E. Romaguera, L. Fayad, M. A. Rodriguez, K. R. Broglio, F. B. Hagemeister, B. Pro, P. McLaughlin, A. Younes, F. Samaniego, A. Goy, et al. High Rate of Durable Remissions After Treatment of Newly Diagnosed Aggressive Mantle-Cell Lymphoma With Rituximab Plus Hyper-CVAD Alternating With Rituximab Plus High-Dose Methotrexate and Cytarabine J. Clin. Oncol., October 1, 2005; 23(28): 7013 - 7023. [Abstract] [Full Text] [PDF]

				T. E. Witzig, S. M. Geyer, I. Ghobrial, D. J. Inwards, R. Fonseca, P. Kurtin, S. M. Ansell, R. Luyun, P. J. Flynn, R. F. Morton, et al. Phase II Trial of Single-Agent Temsirolimus (CCI-779) for Relapsed Mantle Cell Lymphoma J. Clin. Oncol., August 10, 2005; 23(23): 5347 - 5356. [Abstract] [Full Text] [PDF]

				S. M. Ansell and J. Armitage Non-Hodgkin Lymphoma: Diagnosis and Treatment Mayo Clin. Proc., August 1, 2005; 80(8): 1087 - 1097. [Abstract] [PDF]

				M. Dreyling, G. Lenz, E. Hoster, A. Van Hoof, C. Gisselbrecht, R. Schmits, B. Metzner, L. Truemper, M. Reiser, H. Steinhauer, et al. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network Blood, April 1, 2005; 105(7): 2677 - 2684. [Abstract] [Full Text] [PDF]

				R. I. Fisher Mantle Cell Lymphoma: At Last, Some Hope for Successful Innovative Treatment Strategies J. Clin. Oncol., February 1, 2005; 23(4): 657 - 658. [Full Text] [PDF]

				M. B. Maris, B. M. Sandmaier, B. E. Storer, T. Chauncey, M. J. Stuart, R. T. Maziarz, E. Agura, A. A. Langston, M. Pulsipher, R. Storb, et al. Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma Blood, December 1, 2004; 104(12): 3535 - 3542. [Abstract] [Full Text] [PDF]

				W. Brugger, J. Hirsch, F. Grunebach, R. Repp, P. Brossart, W. Vogel, H.-G. Kopp, M. G. Manz, M. Bitzer, G. Schlimok, et al. Rituximab consolidation after high-dose chemotherapy and autologous blood stem cell transplantation in follicular and mantle cell lymphoma: a prospective, multicenter phase II study Ann. Onc., November 1, 2004; 15(11): 1691 - 1698. [Abstract] [Full Text] [PDF]

				A. Bennaceur-Griscelli, J. Bosq, S. Koscielny, F. Lefrere, A. Turhan, N. Brousse, O. Hermine, and V. Ribrag High Level of Glutathione-S-Transferase {pi} Expression in Mantle Cell Lymphomas Clin. Cancer Res., May 1, 2004; 10(9): 3029 - 3034. [Abstract] [Full Text] [PDF]

				K. Belhadj, M.-H. Delfau-Larue, T. Elgnaoui, F. Beaujean, J.-L. Beaumont, C. Pautas, I. Gaillard, Y. Kirova, A. Allain, P. Gaulard, et al. Efficiency of in vivo purging with rituximab prior to autologous peripheral blood progenitor cell transplantation in B-cell non-Hodgkin's lymphoma: a single institution study Ann. Onc., March 1, 2004; 15(3): 504 - 510. [Abstract] [Full Text] [PDF]

				M. Jermann, L. M. Jost, Ch. Taverna, E. Jacky, H. P. Honegger, D. C. Betticher, F. Egli, Th. Kroner, and R. A. Stahel Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study Ann. Onc., March 1, 2004; 15(3): 511 - 516. [Abstract] [Full Text] [PDF]

				J. Mangel, H. A. Leitch, J. M. Connors, R. Buckstein, K. Imrie, D. Spaner, M. Crump, N. Pennell, A. Boudreau, and N. L. Berinstein Intensive chemotherapy and autologous stem-cell transplantation plus rituximab is superior to conventional chemotherapy for newly diagnosed advanced stage mantle-cell lymphoma: a matched pair analysis Ann. Onc., February 1, 2004; 15(2): 283 - 290. [Abstract] [Full Text] [PDF]

				R. I. Fisher, T. P. Miller, and O. A. O'Connor Diffuse Aggressive Lymphoma Hematology, January 1, 2004; 2004(1): 221 - 236. [Abstract] [Full Text] [PDF]

				I. F. Khouri, M.-S. Lee, R. M. Saliba, G. Jun, L. Fayad, A. Younes, B. Pro, S. Acholonu, P. McLaughlin, R. L. Katz, et al. Nonablative Allogeneic Stem-Cell Transplantation for Advanced/Recurrent Mantle-Cell Lymphoma J. Clin. Oncol., December 1, 2003; 21(23): 4407 - 4412. [Abstract] [Full Text] [PDF]

				H. A. Leitch, R. D. Gascoyne, M. Chhanabhai, N. J. Voss, R. Klasa, and J. M. Connors Limited-stage mantle-cell lymphoma Ann. Onc., October 1, 2003; 14(10): 1555 - 1561. [Abstract] [Full Text] [PDF]

				A. M. Gianni, M. Magni, M. Martelli, M. Di Nicola, C. Carlo-Stella, S. Pilotti, A. Rambaldi, S. Cortelazzo, C. Patti, G. Parvis, et al. Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen) Blood, July 15, 2003; 102(2): 749 - 755. [Abstract] [Full Text] [PDF]

				G. Damaj, V. Verkarre, A. Delmer, P. Solal-Celigny, I. Yakoub-Agha, C. Cellier, F. Maurschhauser, R. Bouabdallah, V. Leblond, F. Lefrere, et al. Primary follicular lymphoma of the gastrointestinal tract: a study of 25 cases and a literature review Ann. Onc., April 1, 2003; 14(4): 623 - 629. [Abstract] [Full Text] [PDF]

				E. Zucca, A. Conconi, T.I. Mughal, A.H. Sarris, J.F. Seymour, U. Vitolo, R. Klasa, M. Ozsahin, G.M. Mead, M.A. Gianni, et al. Patterns of Outcome and Prognostic Factors in Primary Large-Cell Lymphoma of the Testis in a Survey by the International Extranodal Lymphoma Study Group J. Clin. Oncol., January 1, 2003; 21(1): 20 - 27. [Abstract] [Full Text] [PDF]

				C. Visco, L. J. Medeiros, D. Jones, T. Smith, M. A. Rodriguez, P. McLaughlin, J. Romaguera, F. Cabanillas, and A. H. Sarris Primary cutaneous non-Hodgkin's lymphoma with aggressive histology: inferior outcome is associated with peripheral T-cell type and elevated lactate dehydrogenase, but not extent of cutaneous involvement Ann. Onc., August 1, 2002; 13(8): 1290 - 1299. [Abstract] [Full Text] [PDF]

				A. Hollender, S. Kvaloy, O. Nome, E. Skovlund, K. Lote, and H. Holte Central nervous system involvement following diagnosis of non-Hodgkin's lymphoma: a risk model Ann. Onc., July 1, 2002; 13(7): 1099 - 1107. [Abstract] [Full Text] [PDF]

				A. K. Gopal, J. G. Rajendran, S. H. Petersdorf, D. G. Maloney, J. F. Eary, B. L. Wood, T. A. Gooley, S. A. Bush, L. D. Durack, P. J. Martin, et al. High-dose chemo-radioimmunotherapy with autologous stem cell support for relapsed mantle cell lymphoma Blood, May 1, 2002; 99(9): 3158 - 3162. [Abstract] [Full Text] [PDF]

				O. M. Howard, J. G. Gribben, D. S. Neuberg, M. Grossbard, C. Poor, M. J. Janicek, and M. A. Shipp Rituximab and CHOP Induction Therapy for Newly Diagnosed Mantle-Cell Lymphoma: Molecular Complete Responses Are Not Predictive of Progression-Free Survival J. Clin. Oncol., March 1, 2002; 20(5): 1288 - 1294. [Abstract] [Full Text] [PDF]

				I. Barista, F. Cabanillas, J. E. Romaguera, I. F. Khouri, Y. Yang, T. L. Smith, S. S. Strom, L. J. Medeiros, and F. B. Hagemeister Is there an increased rate of additional malignancies in patients with mantle cell lymphoma? Ann. Onc., February 20, 2002; 13(2): 318 - 322. [Abstract] [Full Text] [PDF]

				Y. Yatabe, R. Suzuki, K. Tobinai, Y. Matsuno, R. Ichinohasama, M. Okamoto, M. Yamaguchi, J.-i. Tamaru, N. Uike, Y. Hashimoto, et al. Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma: a clinicopathologic comparison of cyclin D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma Blood, April 1, 2000; 95(7): 2253 - 2261. [Abstract] [Full Text] [PDF]

				H. M. Kantarjian, S. O’Brien, T. L. Smith, J. Cortes, F. J. Giles, M. Beran, S. Pierce, Y. Huh, M. Andreeff, C. Koller, et al. Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia J. Clin. Oncol., February 1, 2000; 18(3): 547 - 547. [Abstract] [Full Text] [PDF]