Busulfan, cyclophosphamide, and etoposide as high-dose conditioning regimen in patients with malignant lymphoma

• Published in: Annals of hematology Vol. 81; no. 2; pp. 96 - 102
• Main Authors: Hänel, M, Kröger, N, Sonnenberg, S, Bornhäuser, M, Krüger, W, Kroschinsky, F, Hänel, A, Metzner, B, Birkmann, J, Schmid, B, Hoffknecht, M M, Fiedler, F, Ehninger, G, Zander, A R
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01-02-2002
• Subjects: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Busulfan - administration & dosage; Busulfan - adverse effects; Combined Modality Therapy; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Disease-Free Survival; Etoposide - administration & dosage; Etoposide - adverse effects; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease - drug therapy; Humans; Lymphoma, Non-Hodgkin - drug therapy; Male; Middle Aged; Recurrence; Transplantation Conditioning; Transplantation, Autologous
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-001-0413-8

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.