title: Busulfan, cyclophosphamide, and etoposide as high-dose conditioning regimen in patients with malignant lymphoma.
abstract: We investigated the efficacy and toxicity of the combination of busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP-16) as a preparative regimen prior to autologous hematopoietic stem cell transplantation (ASCT) in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL). Fifty-three patients with recurrent ( n=30), refractory ( n=20), or high-risk ( n=3) lymphoma were enrolled. The 10 patients with HD and 43 with NHL (median age: 46 years, range: 18-64) received busulfan (16 mg/kg), cyclophosphamide (120 mg/kg), and etoposide (30 or 45 mg/kg) followed by ASCT. A total of 50 patients (94%) were consolidated in complete ( n=25) or partial ( n=25) remission, whereas 3 patients had chemoresistant disease before Bu/Cy/VP-16. Thirty-five patients (66%) had received prior radiotherapy (RT) excluding total body irradiation (TBI) as part of the conditioning regimen. The main nonhematological toxicities (grade II-IV according to the Bearman score) in 52 evaluable patients were mucositis (79%) and hepatic toxicity (15%). Severe veno-occlusive disease (VOD) occurred in three patients (5.8%) including one treatment-related death caused by VOD. Overall, treatment-related mortality was 3.8%. After a median follow-up for surviving patients of 21 months (range: 6-118), 20 patients (38%) are in continuous complete remission, 8 patients (15%) are alive in relapse, and 25 patients (47%) died. Probabilities of relapse, event-free survival, and overall survival at 3 years were 63% [95% confidence interval (CI): 48-79%], 31% (95% CI: 17-46%), and 43% (95% CI: 27-59%), respectively. In conclusion, Bu/Cy/VP-16 is an effective and well-tolerated conditioning regimen in patients with HD and NHL. Both toxicity and outcome were not significantly different in patients treated with 30 mg/kg and 45 mg/kg etoposide, respectively. The observed long-term results are even comparable to those published for other established high-dose protocols, including TBI-based regimens. However, further investigations are necessary to evaluate the value of Bu/Cy/VP-16 as a high-dose protocol for malignant lymphoma, especially in patients who have already received extensive RT.
authors.affiliation: Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hänel
authors.forename: N
authors.initials: N
authors.lastname: Kröger
authors.forename: S
authors.initials: S
authors.lastname: Sonnenberg
authors.forename: M
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: W
authors.initials: W
authors.lastname: Krüger
authors.forename: F
authors.initials: F
authors.lastname: Kroschinsky
authors.forename: A
authors.initials: A
authors.lastname: Hänel
authors.forename: B
authors.initials: B
authors.lastname: Metzner
authors.forename: J
authors.initials: J
authors.lastname: Birkmann
authors.forename: B
authors.initials: B
authors.lastname: Schmid
authors.forename: M M
authors.initials: MM
authors.lastname: Hoffknecht
authors.forename: F
authors.initials: F
authors.lastname: Fiedler
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
authors.forename: A R
authors.initials: AR
authors.lastname: Zander
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D002066:Busulfan