Augmented high-dose regimen of cyclophosphamide, carmustine, and etoposide with autologous hematopoietic stem cell transplantation for relapsed and refractory aggressive non-Hodgkin's lymphoma

Progressive disease is the major cause of treatment failure after autologous hematopoietic stem cell transplantation for relapsed or refractory non-Hodgkin's lymphoma. An augmented high-dose regimen of cyclophosphamide 7,200 mg/m(2), carmustine 300-400 mg/m(2), and etoposide 2,400 mg/m(2) (CBV) was developed in an attempt to improve disease control post-transplant. Sixty-seven adult patients received augmented CBV followed by infusion of unpurged autologous peripheral blood stem cells. Thirty seven patients had relapsed after standard chemotherapy, 28 patients had primary refractory disease, and 2 patients had transformed lymphoma in first partial response. Treatment-related mortality was 4%. Actuarial four year overall survival and progression-free survival were 46 +/- 8% and 36 +/- 6%, respectively. Risk factors for disease progression were histologic involvement of marrow by lymphoma and infusion of increased numbers of CD34+ cells per kg in the stem cell autograft. The outcome for patients with relatively chemorefractory disease (defined as 25-49% reduction in tumor volume after salvage chemotherapy) was no different than that for patients with chemosensitive disease. Compared to standard high-dose CBV regimens, augmented CBV does not appear to have substantially improved disease control. Prospective study of the association between inferior progression-free survival and infusion of higher CD34+ cell doses in stem cell autografts is warranted.