Long-term results of a phase-I/II study of sequential high-dose chemotherapy with autologous stem cell transplantation in the initial treatment of aggressive non-Hodgkin's lymphoma

Aims and background: To improve the survival of patients with aggressive non-Hodgkin's lymphoma, we evaluated a risk-adapted therapeutic approach using high-dose (HD) or conventional-dose (CD) chemotherapy (CT) for poor-risk and good-risk patients, respectively. Methods: Twenty patients were treated in each group. In both groups, the first chemotherapy cycle consisted of dexamethasone, vincristine, ifosfamide, and etoposide. Thereafter, the CD or HD patients received 3 or 2 cycles of dexamethasone, vincristine, epirubicin, and cyclophosphamide, respectively, followed by 1 cycle of dexamethasone, carboplatin, and etoposide. In the HD group cyclophosphamide, epirubicin, carboplatin, and etoposide were dose-escalated by a factor of 6, 3, 3, and 3, respectively, as compared to the CD group, and autologous peripheral blood stem cells were administered after each HD-CT cycle. Results: Grade III-IV toxicities were neutropenia and thrombocytopenia (100%), anemia (55%), and stomatitis (30%) in patients with HD-CT, and neutropenia (90%) in patients with CDCT. One toxic death occurred in a patient with HD-CT.The overall response rate was 100% in HD-CT patients, including 70% complete remissions, and 80% in CD-CT patients, including 60% complete remissions. The 10-year overall survival was 55% for patients with HD-CT and 80% for patients with CD-CT. Conclusions: The risk-adapted treatment approach showed tolerable toxicities and was associated with encouraging results.