© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 1, 22-30,
January 3, 2001
© 2001 Oxford University Press
Standard Chemotherapy With or Without High-Dose Chemotherapy for Aggressive Non-Hodgkin's Lymphoma: Randomized Phase III EORTC Study
Affiliations of authors: H. C. Kluin-Nelemans (Department of Hematology), E. M. Noordijk (Department of Radiotherapy), Leiden University Medical Center, The Netherlands; V. Zagonel (Department of Oncology), A. Carbone (Department of Pathology), National Cancer Institute, Aviano, Italy; A. Anastasopoulou, H. Musson, I. Teodorovic, European Organization for Research and Treatment of Cancer (EORTC) Data Center, Brussels, Belgium; D. Bron, Institute Jules Bordet, Brussels; K. J. Roozendaal, Onze Lieve Vrouwen Gasthuis, Amsterdam, The Netherlands; B. Maes (Department of Pathology), J. Thomas (Department of Oncology), University Hospital, Leuven, Belgium; P. Carde, EORTC Lymphoma Group, Institute Gustave-Roussy, Villejuif, France.
Correspondence to present address: Hanneke C. Kluin-Nelemans, M.D., Ph.D., University Hospital Groningen, Department of Hematology, P.O. Box 30001, 9700 RB Groningen, The Netherlands (e-mail: J.C.Kluin-Nelemans{at}int.azg.nl).
Background: The long-term outcome for patients with aggressive non-Hodgkin's lymphoma (NHL) is poor. Consequently, the European Organization for Research and Treatment of Cancer Lymphoma Group designed a prospective randomized trial to investigate whether high-dose chemotherapy plus autologous bone marrow transplantation (ABMT) after standard combination chemotherapy improves long-term survival. Methods: Patients aged 15–65 years with aggressive NHL received three cycles of CHVmP/BV polychemotherapy (i.e., a combination of cyclophosphamide, doxorubicin, teniposide, and prednisone, with bleomycin and vincristine added at mid-cycle). After these three cycles, patients with a complete or partial remission and at that time no lymphoma involvement in the bone marrow were randomly assigned to the ABMT arm (a further three cycles of CHVmP/BV followed by BEAC [i.e., a combination of carmustine, etoposide, cytarabine, and cyclophosphamide] chemotherapy and ABMT) or to the control arm (five more cycles of CHVmP/BV). All statistical tests are two-sided. Results: From December 1990 through October 1998, 311 patients (median age = 44 years) were registered and received the first three cycles of CHVmP/BV, and 194 patients were randomly assigned to the treatment arms. Approximately 70% (140 patients) of these patients were of low or low–intermediate International Prognostic Index (IPI) risk. After a median follow-up of 53 months, an intention-to-treat analysis showed a time to disease progression and overall survival at 5 years of 61% (95% confidence interval [CI] = 51% to 72%) and 68% (95% CI = 57% to 79%), respectively, for the ABMT arm and 56% (95% CI = 45% to 67%) and 77% (95% CI = 67% to 86%), respectively, for the control arm. Differences between arms were not statistically significant. A subset analysis on IPI risk groups, although too small for reliable statistical analysis, yielded similar results. Conclusions: Standard combination therapies remain the best choice for most patients with aggressive NHL. We recommend that patients with IPI low or low–intermediate risk not be subjected to high-dose chemotherapy and ABMT as a first-line therapy.
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