High-dose chemotherapy (HDC) with autologous stem-cell support (ASCS) is commonly used to treat patients with relapsed or high risk but chemosensitive non-Hodgkin's lymphoma (NHL) and Hodgkin's Disease (HD). However, the optimum HDC regimen for these patients has not been defined. CEB or BEAM are among the most commonly used regimens, but they have not been compared in a randomized prospective study. At our center, CEB was the preferred regimen until Dec 2002 and BEAM has been the preferred regimen since. We compared pre-treatment characteristics and post HDC outcomes in 219 consecutive patients undergoing single HDC+ASCS for NHL/HD at our center who received BEAM or CEB as the HDC regimen. BEAM (BCNU 300mg/m2, Etoposide 800 mg/m2, Cytarabine 1600 mg/m2, Melphalan 140 mg/m2) was used in 110 patients and 109 patients received CEB (Cyclophosphamide 6000mg/m2, Etoposide 2000mg/m2, BCNU 600mg/m2). The groups were comparable with respect to pre-treatment characteristics: median age (48 vs 52), gender (M 66% vs 64%), diagnosis (NHL 75% vs 81%), number of prior regimens (median=2 for both),stage at diagnosis, disease status pre-HDC, and median CD34+ cell dose/kg infused (5.6 x 10e6 vs 5.4x 10e6), KPS (≥90 vs <90) (p=NS for all). Median follow-up from HDC was longer in CEB patients (841 days) than in BEAM patients (443 days).Estimated Kaplan-Meier probabilities of progression-free survival (PFS) at 12 months and 24 months post HDC were 66.3%, 49.3% for BEAM and 60.2%, 55.1% for CEB (p=NS). The probability of overall survival (OS) at 12 and 24 months was 79.2%, 68.7% respectively for BEAM and 68.6%, 62.9% for CEB (p=NS). Transplant-related mortality (TRM) at 12m was 4.5% for BEAM versus 6.4% for CEB (p=NS). A Cox proportional hazards analysis was performed to assess the effect on OS, PFS and TRM of the following variables: regimen (BEAM vs CEB), diagnosis (HD vs NHL), age, gender, KPS, number of prior Rx regimens,stage at diagnosis, stage at treatment, disease status at transplant, CD34+ cell dose. On multivariate analysis, the following statisically significant associations were observed for the three outcome variables. PFS: age, gender, number of prior regimens,disease status at transplant. OS: age, gender, diagnosis, disease status at transplant. TRM: none. Females and patients with HD had better OS and PFS than males and NHL patients respectively. Conditioning regimen did not correlate with outcome for PFS, OS or TRM.The rate of severe mucositis (as defined by use of infusional opiate therapy during the first 25 days following HDC+ASCS) was significantly higher with CEB than BEAM (53% vs 47%, p=0.040). The rate of BCNU induced pnemonitis syndrome (as measured by prednisone use during first 30–120 days following HDC+ASCS and/or hospital readmission before day +120) was not significantly different between the two regimen groups. In summary, analysis of this sequential series of well matched patients receiving BEAM or CEB for HDC+ASCS for NHL or HD indicates that survival outcomes are comparable and BEAM is associated with a significant lower incidence of mucositis