Summary:Relapse after transplant for malignant lymphomas remains the main cause of treatment failure. Most conditioning regimens contain total body irradiation (TBI). We investigated the toxicity and efficacy of an intensified chemotherapy conditioning regimen without TBI in patients with relapsed or high-risk malignant lymphoma who had received prior radiation therapy and were therefore not eligible for TBI. Twenty patients with a median age of 38 (18-56) and relapsed or highrisk malignant non-Hodgkin's lymphoma (NHL, n = 16) or Hodgkin's disease (HD, n = 4) underwent high-dose chemotherapy consisting of busulfan (16 mg/kg), cyclophosphamide (120 mg/kg) and etoposide 30 mg/kg (n = 8) or 45 mg/kg (n = 12) followed by peripheral stem cell support (n = 14), autologous bone marrow (n = 3), allogeneic (n = 2) or syngeneic (n = 1) transplantation. All but two had chemosensitive disease before high-dose chemotherapy. The main toxicity -according to the Bearman score -was mucositis II in 18 (90%) patients; five patients (25%) suffered a grade I hepatic toxicity. GI toxicity I occurred in three (15%) and renal toxicity I in two patients (10%). Sixty percent of the patients developed transient dermatitis with erythema and three of them (15%) had skin desquamation; one patient experienced asymptomatic pancreatitis. Toxicity was slightly higher in patients treated with 45 mg/kg etoposide. One patient (5%) died of treatment-related venoocclusive disease. After a median follow-up of 50 months (24-84) the disease-free and overall survival were 50% and 55%. One of the nine relapsing patients developed secondary AML 18 months after transplant. High-dose busulfan, cyclophosphamide and etoposide is an effective regimen resulting in long-term disease-free survival in 50% of patients with relapsed malignant lymphoma and prior radiation therapy. The toxicity is moderate with a low treatment-related mortality (5%). Keywords: malignant lymphoma; high-dose chemotherapy; etoposide; busulfan; cyclophosphamide. High-dose chemotherapy and/or radiotherapy with peripheral blood stem cell support is increasingly used in patients with high-risk or relapsed malignant non-Hodgkin's lymphoma.1-3 Recently, a randomized trial confirmed the superiority of high-dose chemotherapy followed by autologous bone marrow transplantation over standard salvage therapy for relapsing chemosensitive non-Hodgkin's lymphoma. 4 Total body irradiation (TBI) is part of many frequently used conditioning regimens. The most frequent single cause of treatment failure has been relapse. In an attempt to decrease the relapse rate, etoposide was added to the TBI/cyclophosphamide regimen because of its known activity against lymphoma. [5][6][7] However, patients with prior dose-limiting radiation therapy need alternative radiationfree preparative regimens. The combination of busulfan plus cyclophosphamide (Bu/Cy) has been widely used in patients with hematological malignancies. Initially, studies using busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) provided an effective ...