Efficacy and toxicity of a CCNU-containing high-dose chemotherapy regimen followed by autologous hematopoietic cell transplantation in relapsed or refractory Hodgkin's disease

High-dose CBV (cyclophosphamide, carmustine, and etoposide) in combination with autologous HCT achieves survival rates of approximately 50% at 5 years in recurrent or refractory Hodgkin's disease (HD). However, carmustine (BC NU) dose-dependent pulmonary toxicity occurs in 20% to 30% of patients. A d ecreased incidence of interstitial pneumonitis as well as a possible benefi t in efficacy has been reported with lomustine (CCNU) compared to BCNU in t he standard dose setting. In a dose-escalation study, we substituted CCNU f or BCNU in the CBV regimen for 16 patients with HD (n=12) or non-Hodgkin's lymphoma (n=4). Based on the promising results, an additional 47 consecutiv e patients with RD were treated with the following regimen: CCNU (15 mg/kg) orally on day -6, etoposide (60 mg/kg) intravenously on day -4, and cyclop hosphamide (100 mg/kg) intravenously on day -2. Peripheral blood progenitor cells and/or bone marrow were infused on day 0. With a median follow-up fo r the surviving patients of 3.2 years (range, 0.8-9.9 years), the 3-year ov erall survival rate was 57% (CI, +/- 15%), event-free survival was 52% (CI, +/- 14%), and freedom from progression was 68% (CI, +/- 14%). There were 2 1 deaths, 10 due to HD. Six patients died due to respiratory failure. Inter stitial pneumonitis occurred in 63% of patients and could not be correlated with prior chest radiotherapy. This regimen demonstrated survival rates si milar to those of historical studies that used the CBV regimen. However, th e incidence of interstitial pneumonitis was in excess of expected.