Journal of Clinical Oncology, Vol 20, Issue 22
(November), 2002: 4413-4419
© 2002 American Society for Clinical Oncology
Randomized Study to Evaluate the Use of High-Dose Therapy as Part of Primary Treatment for "Aggressive" Lymphoma
Ulrich Kaiser,
Irmgard Uebelacker,
Ulrich Abel,
Josef Birkmann,
Lorenz Trumper,
Harald Schmalenberg,
Tunca Karakas,
Bernd Metzner,
Dieter K. Hossfeld,
Helge G. Bischoff,
Astrid Franke,
Marcel Reiser,
Peter Muller,
Luisa Mantovani,
Marc Grundeis,
Frank Rothmann,
Cay-Uwe von Seydewitz,
Rolf M. Mesters,
Ernst U. Steinhauer,
Dorothea Krahl,
Kurt Schumacher,
Michael Kneba,
Michael Baudis,
Norbert Schmitz,
Rudiger Pfab,
Hubert Koppler,
Reza Parwaresch,
Michael Pfreundschuh,
Klaus Havemann
From the Departments of Hematology and Oncology, Universitätsklinikum Marburg, Klinikum Nürnberg, Universitätsklinikum Homburg, Universitätsklinikum Jena, Universitätsklinikum Ulm, Klinikum Oldenburg, Universitätsklinikum Hamburg, Thoraxklinik Heidelberg-Rohrbach, Universitätsklinikum Magdeburg, Universitätsklinikum Köln, Zentralklinikum Augsburg, Universitätsklinikum Leipzig, Universitätsklinikum Leipzig, Klinikum Chemnitz, Klinikum Potsdam, Krankenhaus Hamburg-Altona, Universitätsklinikum Münster, Klinikum Kassel, Humboldt-Universität Berlin, Robert-Bosch Krankenhaus Stuttgart, Universitätsklinikum Göttingen, Universitätsklinikum Heidelberg, Universitätsklinikum Kiel, Klinikum Minden, Universitätsklinikum Rostock, Universitätsklinikum Zürich, Klinikum Karlsruhe, Klinikum Hagen, Klinikum Herford, Klinikum Lemgo, Universitätsklinikum Lund, Klinikum Mönchengladbach, Universitätsklinikum Uppsala, Universitätsklinikum Aachen, Diakonissenkrankenhaus Bremen, Klinikum Cottbus, Klinikum Darmstadt, Klinikum Eschweiler, Diakoniekrankenhaus Freiburg, Klinikum Münchberg, Klinikum Schwenningen, Klinikum Schweinfurt, Klinikum Trier, and Klinikum Wolfsburg; the Institute of Medical Statistics, Universität Heidelberg; and the Institute of Hematopathology, Universität Kiel, Germany.
Address reprint requests to Ulrich Kaiser, MD, St Bernward Krankenhaus, Klinik für Hämatologie, Onkologie und Immunologie, Treibestrasse 9, D-31134 Hildesheim, Germany; email: pd.dr.u.kaiser{at}bernward-khs.de
PURPOSE: This trial of the German High-Grade Non-Hodgkin’s Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study.
PATIENTS AND METHODS: Three hundred twelve patients with "aggressive" non-Hodgkin’s lymphoma aged  60 years with elevated serum lactate dehydrogenase levels were included from 1990 to 1997. Patients with at least a minor response after two cycles of CHOEP (CHOP + etoposide 3 x 100 mg/m2) were to receive three further cycles of CHOEP followed by IF radiotherapy (arm A) or one further cycle of CHOEP followed by autologous stem-cell transplantation and IF radiotherapy (arm B).
RESULTS: Among 158 patients randomized to arm B, 103 (65%) received HDT. The complete remission rate at the end of treatment was 62.9% in arm A and 69.9% in arm B. With a median observation time of 45.5 months, overall survival for all 312 patients was 63% after 3 years (63% for arm A, 62% for arm B; P = .68). Event-free survival was 49% for arm A versus 59% for arm B (P = .22). Relapse in arm B was associated with a significantly worse survival rate than relapse in arm A (P < .05). Relapse after HDT occurred early (median interval, 3 months). Six patients developed secondary neoplasia, three in arm A and three in arm B.
CONCLUSION: Results of the randomized trial comparing CHOP-like chemotherapy with early HDT do not support the use of HDT with carmustine, etoposide, cytarabine, and melphalan following shortened standard chemotherapy.
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