Background: Adequate cytoreduction with cisplatin-based chemotherapy is commonly used prior to high dose chemotherapy and autologous stem cell support (HDC-ASCS) among R/R aggressive lymphoma patients. However, it is associated with significant cisplatin-related toxicities. Swapping cisplatin with another platinum agent could decrease treatment related toxicities. Methods: To this end, we developed the DHAC regimen and retrospectively studied the clinical outcome of patients receiving this regimen between 06/00 and 07/12 (N = 40). Outcomes included overall response rate (ORR), overall survival (OS) and treatment related toxicities. DHAC consisted of: Dexamethasone at 15mg/m²/dose po q6 hrs x 10 doses, High-dose Cytarabine at 3gr/m² (1.5gr/m² if > 50 yrs old) intravenously (IV) q12 hrs for 4 doses and Carboplatin at 200mg/m² IV q24hrs for 2 doses. When utilized, patients received rituximab at 375mg/m², 24-48 hrs prior to each DHAC cycle. Growth factor support and anti-microbial prophylaxis was implemented 24 hrs post chemotherapy. The regimen was repeated every 21 days. Responses were assessed after 2 cycles with patients proceeding to HDC-ASCS once optimal cytoreduction was obtained. Results: Median age 61yrs; 58% male; 28% had diffuse large B-cell lymphoma (DLBCL), 27% transformed DLBCL, 7.5% follicular lymphoma (FL); 7.5% Hodgkin lymphoma (HL), 12.5% chronic lymphocytic leukemia (CLL), and 10% mantle cell lymphoma (MCL). Median number of prior therapies was 2 (0-6). Median number of DHAC ± R cycles was 2. The ORR was 52% with a complete response (CR) rate of 38%. HDC-ASCS was performed in 38%. Refractory disease to prior therapy was associated with lower CR rates (P = 0.003) and shorter OS (210 days vs. not reached) (P = 0.049). DHAC ± R was well tolerated with manageable grade 3/4 hematologic toxicities. Conclusions: DHAC ± R is a safe and effective salvage regimen for relapsed/refractory aggressive lymphoma. Refractory disease to prior therapy was associated with poor clinical response to this regimen and shorter OS, stressing the need to develop alternative therapeutic strategies for this subgroup of aggressive lymphoma patients.