Background High-dose chemotherapy followed by autologous bonemarrow transplantation is a therapeutic option for patientswith chemotherapy-sensitive non-Hodgkin's lymphoma who haverelapses. In this report we describe a prospective randomizedstudy of such treatment.
Methods A total of 215 patients with relapses of non-Hodgkin'slymphoma were treated between July 1987 and June 1994. All patientsreceived two courses of conventional chemotherapy. The 109 patientswho had a response to chemotherapy were randomly assigned toreceive four courses of chemotherapy plus radiotherapy (54 patients)or radiotherapy plus intensive chemotherapy and autologous bonemarrow transplantation (55 patients).
Results The overall rate of response to conventional chemotherapywas 58 percent; among patients with relapses after chemotherapy,the response rate was 64 percent, and among those with relapsesduring chemotherapy, the response rate was 21 percent. Therewere three deaths from toxic effects among the patients in thetransplantation group, and none among those in the group receivingchemotherapy without transplantation. The two groups did notdiffer in terms of prognostic factors. The median follow-uptime was 63 months. The response rate was 84 percent after bonemarrow transplantation and 44 percent after chemotherapy withouttransplantation. At five years, the rate of event-free survivalwas 46 percent in the transplantation group and 12 percent inthe group receiving chemotherapy without transplantation (P= 0.001), and the rate of overall survival was 53 and 32 percent,respectively (P = 0.038).
Conclusions As compared with conventional chemotherapy, treatmentwith high-dose chemotherapy and autologous bone marrow transplantationincreases event-free and overall survival in patients with chemotherapy-sensitivenon-Hodgkin's lymphoma in relapse.
Source Information
From the Department of Medical Oncology, Bone Marrow Transplantation and Biostatistics Unit, Centre Léon Bérard, Lyon, France (T.P., P.B., F.C.); Universita degli Studi La Sapienza, Rome (C. Guglielmi, F.M.); the Doctor Daniel Den Hoed Cancer Center, Rotterdam, the Netherlands (A.H.); Antonie Van Leeuwenhoek Huis, the Netherlands Cancer Center Institute, Amsterdam (R.S.); the Academic Medical Center, Amsterdam (H.V.D.L.); Institut Jules Bordet, Brussels, Belgium (D.B.); University Hospital Dijkzigt, Rotterdam, the Netherlands (P.S.); Hôpital Saint Louis, Paris (C. Gisselbrecht); Hôpital Jean Minjoz, Besançon, France (J.-Y.C.); Centre Hospitalier Régional Universitaire de Nantes, Hôpital de l'Hôtel Dieu, Nantes, France (J.-L.H.); and Centre Hospitalier Lyon-Sud, Pierre Benite, France (B.C.).
Address reprint requests to Prof. Philip at the Centre Régional de Lutte contre le Cancer Léon Bérard, 28 rue Laënnec, 69373 Lyon CEDEX 08, France.
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(2005). Diffuse Large B-Cell Lymphoma: Risk Stratification and Management of Relapsed Disease. ASH Education Book
2005: 252-259
[Abstract][Full Text]
Lenz, G., Dreyling, M., Schiegnitz, E., Haferlach, T., Hasford, J., Unterhalt, M., Hiddemann, W.
(2004). Moderate Increase of Secondary Hematologic Malignancies After Myeloablative Radiochemotherapy and Autologous Stem-Cell Transplantation in Patients With Indolent Lymphoma: Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group. JCO
22: 4926-4933
[Abstract][Full Text]
Mounier, N., Gisselbrecht, C., Briere, J., Haioun, C., Feugier, P., Offner, F., Recher, C., Stamatoullas, A., Morschhauser, F., Macro, M., Thieblemont, C., Sonet, A., Fabiani, B., Reyes, F., On behalf of the Groupe d'Etude des Lymphomes de l,
(2004). 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 Oncol
15: 1790-1797
[Abstract][Full Text]
Freytes, C. O., Loberiza, F. R., Rizzo, J. D., Bashey, A., Bredeson, C. N., Cairo, M. S., Gale, R. P., Horowitz, M. M., Klumpp, T. R., Martino, R., McCarthy, P. L., Molina, A., Pavlovsky, S., Pecora, A. L., Serna, D. S., Tsai, T., Zhang, M.-J., Vose, J. M., Lazarus, H. M., van Besien, K.
(2004). Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry. Blood
104: 3797-3803
[Abstract][Full Text]
Lenz, G., Dreyling, M., Schiegnitz, E., Forstpointner, R., Wandt, H., Freund, M., Hess, G., Truemper, L., Diehl, V., Kropff, M., Kneba, M., Schmitz, N., Metzner, B., Pfirrmann, M., Unterhalt, M., Hiddemann, W.
(2004). Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. Blood
104: 2667-2674
[Abstract][Full Text]
Rodriguez, J., Caballero, M. D., Gutierrez, A., Solano, C., Arranz, R., Lahuerta, J. J., Sierra, J., Gandarillas, M., Perez-Simon, J. A., Zuazu, J., Lopez-Guillermo, A., Sureda, A., Carreras, E., Garcia-Larana, J., Marin, J., Garcia, J. C., Fernandez de Sevilla, A., Rifon, J., Varela, R., Jarque, I., Albo, C., Leon, A., SanMiguel, J., Conde, E.
(2004). Autologous stem-cell transplantation in diffuse large B-cell non-Hodgkin's lymphoma not achieving complete response after induction chemotherapy: the GEL/TAMO experience. Ann Oncol
15: 1504-1509
[Abstract][Full Text]
Straka, C., Oduncu, F., Hinke, A., Einsele, H., Drexler, E., Schnabel, B., Arseniev, L., Walther, J., Konig, A., Emmerich, B.
(2004). Responsiveness to G-CSF before leukopenia predicts defense to infection in high-dose chemotherapy recipients. Blood
104: 1989-1994
[Abstract][Full Text]
Mounier, N., Gisselbrecht, C., Briere, J., Haioun, C., Feugier, P., Offner, F., Recher, C., Stamatoullas, A., Morschhauser, F., Macro, M., Thieblemont, C., Sonet, A., Fabiani, B., Reyes, F.
(2004). 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. JCO
22: 2826-2834
[Abstract][Full Text]
Zander, A.R., Kroger, N., Schmoor, C., Kruger, W., Mobus, V., Frickhofen, N., Metzner, B., Schultze, W., Berdel, W.E., Koenigsmann, M., Thiel, E., Wandt, H., Possinger, K., Trumper, L., Kreienberg, R., Carstensen, M., Schmidt, E.H., Janicke, F., Schumacher, M., Jonat, W.
(2004). High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Support Compared With Standard-Dose Chemotherapy in Breast Cancer Patients With 10 or More Positive Lymph Nodes: First Results of a Randomized Trial. JCO
22: 2273-2283
[Abstract][Full Text]
Escalon, M. P., Champlin, R. E., Saliba, R. M., Acholonu, S. A., Hosing, C., Fayad, L., Giralt, S., Ueno, N. T., Maadani, F., Pro, B., Donato, M., McLaughlin, P., Khouri, I. F.
(2004). Nonmyeloablative Allogeneic Hematopoietic Transplantation: A Promising Salvage Therapy for Patients With Non-Hodgkin's Lymphoma Whose Disease Has Failed a Prior Autologous Transplantation. JCO
22: 2419-2423
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Kewalramani, T., Zelenetz, A. D., Nimer, S. D., Portlock, C., Straus, D., Noy, A., O'Connor, O., Filippa, D. A., Teruya-Feldstein, J., Gencarelli, A., Qin, J., Waxman, A., Yahalom, J., Moskowitz, C. H.
(2004). Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood
103: 3684-3688
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Childs, R. W.
(2004). Evolving trends in hematopoietic cell transplantation for solid tumors: tempering enthusiasm with clinical reality. Ann Oncol
15: 543-544
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Gratwohl, A., Baldomero, H., Demirer, T., Rosti, G., Dini, G., Ladenstein, R., Urbano-Ispizua, A.
(2004). Hematopoetic stem cell transplantation for solid tumors in Europe. Ann Oncol
15: 653-660
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Jermann, M., Jost, L. M., Taverna, Ch., Jacky, E., Honegger, H. P., Betticher, D. C., Egli, F., Kroner, Th., Stahel, R. A.
(2004). Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol
15: 511-516
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Izutsu, K., Kanda, Y., Ohno, H., Sao, H., Ogawa, H., Miyazaki, Y., Kawa, K., Kodera, Y., Kato, S., Morishima, Y., Hirai, H.
(2004). Unrelated bone marrow transplantation for non-Hodgkin lymphoma: a study from the Japan Marrow Donor Program. Blood
103: 1955-1960
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Andre, M., Mounier, N., Leleu, X., Sonet, A., Brice, P., Henry-Amar, M., Tilly, H., Coiffier, B., Bosly, A., Morel, P., Haioun, C., Gaulard, P., Reyes, F., Gisselbrecht, C., the Groupe d'Etude des Lymphomes de l'Adulte,
(2004). Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients. Blood
103: 1222-1228
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Horwitz, S. M., Negrin, R. S., Blume, K. G., Breslin, S., Stuart, M. J., Stockerl-Goldstein, K. E., Johnston, L. J., Wong, R. M., Shizuru, J. A., Horning, S. J.
(2004). Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma. Blood
103: 777-783
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Fisher, R. I., Miller, T. P., O'Connor, O. A.
(2004). Diffuse Aggressive Lymphoma. ASH Education Book
2004: 221-236
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Rodriguez, J., Caballero, M. D., Gutierrez, A., Marin, J., Lahuerta, J. J., Sureda, A., Carreras, E., Leon, A., Arranz, R., Fernandez de Sevilla, A., Zuazu, J., Garcia-Larana, J., Rifon, J., Varela, R., Gandarillas, M., SanMiguel, J., Conde, E.
(2003). High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience. Ann Oncol
14: 1768-1775
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Re, A., Cattaneo, C., Michieli, M., Casari, S., Spina, M., Rupolo, M., Allione, B., Nosari, A., Schiantarelli, C., Vigano, M., Izzi, I., Ferremi, P., Lanfranchi, A., Mazzuccato, M., Carosi, G., Tirelli, U., Rossi, G.
(2003). High-Dose Therapy and Autologous Peripheral-Blood Stem-Cell Transplantation As Salvage Treatment for HIV-Associated Lymphoma in Patients Receiving Highly Active Antiretroviral Therapy. JCO
21: 4423-4427
[Abstract][Full Text]
Abrey, L. E., Moskowitz, C. H., Mason, W. P., Crump, M., Stewart, D., Forsyth, P., Paleologos, N., Correa, D. D., Anderson, N. D., Caron, D., Zelenetz, A., Nimer, S. D., DeAngelis, L. M.
(2003). Intensive Methotrexate and Cytarabine Followed by High-Dose Chemotherapy With Autologous Stem-Cell Rescue in Patients With Newly Diagnosed Primary CNS Lymphoma: An Intent-to-Treat Analysis. JCO
21: 4151-4156
[Abstract][Full Text]
Lister, T. A.
(2003). High-Dose Therapy for Follicular Lymphoma Revisited: Not If, but When?. JCO
21: 3894-3896
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Schouten, H. C., Qian, W., Kvaloy, S., Porcellini, A., Hagberg, H., Johnsen, H. E., Doorduijn, J. K., Sydes, M. R., Kvalheim, G.
(2003). High-Dose Therapy Improves Progression-Free Survival and Survival in Relapsed Follicular Non-Hodgkin's Lymphoma: Results From the Randomized European CUP Trial. JCO
21: 3918-3927
[Abstract][Full Text]
Hamlin, P. A., Zelenetz, A. D., Kewalramani, T., Qin, J., Satagopan, J. M., Verbel, D., Noy, A., Portlock, C. S., Straus, D. J., Yahalom, J., Nimer, S. D., Moskowitz, C. H.
(2003). Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma. Blood
102: 1989-1996
[Abstract][Full Text]
Laport, G. G., Levine, B. L., Stadtmauer, E. A., Schuster, S. J., Luger, S. M., Grupp, S., Bunin, N., Strobl, F. J., Cotte, J., Zheng, Z., Gregson, B., Rivers, P., Vonderheide, R. H., Liebowitz, D. N., Porter, D. L., June, C. H.
(2003). Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation. Blood
102: 2004-2013
[Abstract][Full Text]
Lemoli, R. M., de Vivo, A., Damiani, D., Isidori, A., Tani, M., Bonini, A., Cellini, C., Curti, A., Gugliotta, L., Visani, G., Fanin, R., Baccarani, M.
(2003). Autologous transplantation of granulocyte colony-stimulating factor-primed bone marrow is effective in supporting myeloablative chemotherapy in patients with hematologic malignancies and poor peripheral blood stem cell mobilization. Blood
102: 1595-1600
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Spaepen, K., Stroobants, S., Dupont, P., Vandenberghe, P., Maertens, J., Bormans, G., Thomas, J., Balzarini, J., De Wolf-Peeters, C., Mortelmans, L., Verhoef, G.
(2003). Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation. Blood
102: 53-59
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Martelli, M., Gherlinzoni, F., De Renzo, A., Zinzani, P. L., De Vivo, A., Cantonetti, M., Falini, B., Storti, S., Meloni, G., Rizzo, M., Molinari, A. L., Lauria, F., Moretti, L., Lauta, V. M., Mazza, P., Guardigni, L., Pescarmona, E., Pileri, S.A., Mandelli, F., Tura, S.
(2003). Early Autologous Stem-Cell Transplantation Versus Conventional Chemotherapy as Front-Line Therapy in High-Risk, Aggressive Non-Hodgkin's Lymphoma: An Italian Multicenter Randomized Trial. JCO
21: 1255-1262
[Abstract][Full Text]
Metayer, C., Curtis, R. E., Vose, J., Sobocinski, K. A., Horowitz, M. M., Bhatia, S., Fay, J. W., Freytes, C. O., Goldstein, S. C., Herzig, R. H., Keating, A., Miller, C. B., Nevill, T. J., Pecora, A. L., Rizzo, J. D., Williams, S. F., Li, C.-Y., Travis, L. B., Weisdorf, D. J.
(2003). Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study. Blood
101: 2015-2023
[Abstract][Full Text]
Shi, J., Feng, Y., Goulet, A.-C., Vaillancourt, R. R., Sachs, N. A., Hershey, J. W., Nelson, M. A.
(2003). The p34cdc2-related Cyclin-dependent kinase 11 Interacts with the p47 Subunit of Eukaryotic Initiation Factor 3 during Apoptosis. J. Biol. Chem.
278: 5062-5071
[Abstract][Full Text]
Takeyama, K., Ogura, M., Morishima, Y., Kasai, M., Kiyama, Y., Ohnishi, K., Mitsuya, H., Kawano, F., Masaki, Y., Sasaki, T., Chou, T., Yokozawa, T., Tobinai, K.
(2003). 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
33: 78-85
[Abstract][Full Text]
A correction has been published: N Engl J Med 1996;334(15):990.
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