The purpose of this trial was to evaluate the efficacy and the tolerance of high-dose therapy with autologous stem cell transplantation as part of front-line therapy in Hodgkin's disease for patients with both adverse prognostic factors: high tumor burden at presentation and slow response to initial chemotherapy.In a prospective one-center study, 20 consecutive patients with slow response (tumor reduction0.45 at T5-T6) (6 pts) or both stage IV + LMI (7 pts). Median time between diagnosis and autotransplantation was 5 months. Intensive therapy consisted of either CBV (cyclophosphamide 1.5 g/m2×4, BCNU 300 mg/m2, etoposide 200 mg/m2×3) (12 pts) or cyclophosphamide 120 mg/kg + 12 Gy total body irradiation for 8 patients with diffuse bone or lung involvement. For pts treated with CBV, 40 Gy involved field radiotherapy was performed after hematological recovery.Median duration of neutropenia was 16 days (9-21). Neither veno-occlusive disease, nor interstitial pneumonitis nor toxic death were observed. Seventeen pts are alive with no progression of the disease (16/16 in partial response after initial chemotherapy, 1/4 with refractory disease). Three pts with refractory disease before autotransplantation died from progressive disease. The actuarial EFS is 84.7% with a median follow-up of 23 months (8 to 52).We conclude that early intensive therapy with autotransplantation is well tolerated and effective, but given the results of conventional HD therapies, it has to be restricted for very selected patients.