For personal use. Only reproduce with permission from The Lancet Publishing Group. ARTICLES THE LANCET • Vol 359 • June 15, 2002 • www.thelancet.com 2065 Summary Background High-dose chemotherapy followed by trans- plantation of autologous haemopoietic stem cells (BEAM- HSCT) is frequently used to treat patients with relapsed Hodgkin’s disease. We aimed to compare this treatment with conventional aggressive chemotherapy without stem-cell transplantation (Dexa-BEAM). Methods 161 patients between 16 and 60 years of age with relapsed Hodgkin’s disease were randomly assigned two cycles of Dexa-BEAM (dexamethasone and carmustine, etoposide, cytarabine, and melphalan) and either two further courses of Dexa-BEAM or high-dose BEAM and trans- plantation of haemopoietic stem cells. Only patients with chemosensitive disease (complete or partial remission after two courses of Dexa-BEAM) proceeded to further treatment. The primary endpoint was freedom from treatment failure for patients with chemosensitive disease. Analysis was per protocol. Findings 17 patients were excluded from the study after randomisation (ten given Dexa-BEAM and seven given BEAM-HSCT). Median follow-up was 39 months (IQR 3–78). Freedom from treatment failure at 3 years was significantly better for patients given BEAM-HSCT (55%) than for those on Dexa-BEAM (34%; difference –21%, 95% CI –39·87 to –2·13; p=0·019). Overall survival of patients given either treatment did not differ significantly. Interpretation High-dose BEAM and transplantation of haemopoietic stem cells improves freedom from treatment failure in patients with chemosensitive first relapse of Hodgkin’s disease irrespective of length of initial remission. Lancet 2002; 359: 2065–71 Introduction Patients with advanced Hodgkin’s disease have an excellent outlook if treated with modern chemotherapy with or without radiotherapy. 1–3 Patients who relapsed after first-line chemotherapy can achieve further remissions with salvage treatment; 4–7 the chance of cure, however, is limited, and will depend on many prognostic factors, such as length of initial remission, age, type of treatment previously received, presence of B-symptoms (fever, night sweats, weight loss >10% of previous bodyweight), and stage. 8–10 Disease status is the most important factor predicting outcome of patients scheduled to receive high-dose chemotherapy and autologous stem- cell transplantation. 11,12 What is the optimum type of salvage treatment, and does high-dose chemotherapy have any benefit compared with other forms of salvage treatment, not needing transplantation of haemopoietic stem cells? To address this latter question, we prospectively compared aggressive conventional chemotherapy (Dexa-BEAM) with high- dose chemotherapy and autologous stem-cell trans- plantation (BEAM-HSCT) in patients with relapsed Hodgkin’s disease responding to salvage chemotherapy. Patients and methods Patients Patients 16–60 years of age were eligible for the study if they had received chemotherapy for advanced Hodgkin’s disease and had biopsy-proven relapse. We included patients with stage I or II disease at relapse if they presented with additional risk factors (bulky mediastinum, involvement of three or more lymph-node regions, extranodal disease, or erythrocyte sedimentation rate >30 mm), or if they had shown stage III or IV disease early in the course of disease before enrolment. Histological verification of relapse was not mandatory for patients with unequivocal progressive intrathoracic or abdominal disease. Other criteria for eligibility were Karnofsky performance score above 70% and adequate cardiac, pulmonary, renal, and liver function. We excluded patients if they were HIV positive, had infection unresponsive to treatment, or had previously been treated with Dexa-BEAM (dexamethasone and carmustine, etoposide, cytarabine, and melphalan), 6 mini-BEAM, 13 or high-dose chemotherapy. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial Norbert Schmitz, Beate Pfistner, Michael Sextro, Markus Sieber, Angelo M Carella, Matthias Haenel, Friederike Boissevain, Reinhart Zschaber, Peter Müller, Hartmut Kirchner, Andreas Lohri, Susanne Decker, Bettina Koch, Dirk Hasenclever, Anthony H Goldstone, Volker Diehl, for the German Hodgkin’s Lymphoma Study Group (GHSG) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation (EBMT) Department of Internal Medicine II, University of Kiel, Kiel, Germany (Prof N Schmitz MD); Medizinische Klinik I, University of Cologne, Cologne, Germany (B Pfistner PhD, M Sextro MD, M Sieber MD, B Koch, Prof V Diehl MD); Ospedale San Martino, Genoa, Italy (Prof A M Carella MD); Klinikum Chemnitz, Chemnitz, Germany (M Haenel MD); Klinikum Nürnberg, Nürnberg, Germany (F Boissevain MD); Department of Oncology and Haematology, Hamburg-Eppendorf, Hamburg, Germany (Prof R Zschaber MD); Zentralklinikum Augsburg, Augsburg, Germany (P Müller MD); Krankenhaus Siloah, Hannover, Germany (H Kirchner MD); SAKK Bern, Bern, Switzerland (A Lohri MD); Department of Haematology and Oncology, University of Rostock, Rostock, Germany (S Decker MD); Institute of Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany (D Hasenclever PhD); and Department of Haematology, University College London Hospitals, London, UK (A H Goldstone FRCPath) Correspondence to: Prof Norbert Schmitz, Department of Haematology, AK St Georg, Lohmühlenstr 5, 20099 Hamburg, Germany (e-mail: Norbert.Schmitz@ak-stgeorg.lbk-hh.de)