As stated in the guidelines, autotransplantation cannot generally be put into first-line treatment and should only be considered for relapsed patients. This is primarily because post-transplant complications significantly increase patient prevalence and because survival is the same for chemotherapy and autograft recipients. A 2008 meta-analysis, which included data from 15 randomized controlled trials, had a total of 3079 patients treated for aggressive non-Hodgkin’s lymphoma [1]. Treatment-related mortality, disease-free progression, and overall survival were the same whether patients received conventional or high-dose chemotherapy followed by autologous transplantation. Randomized trials have shown that first-line autotransplantation has similar survival rates to post-relapse autotransplantation, even in high-risk disease. An intergroup trial (S9704) recruited 397 patients with high-intermediate-risk and high-risk International Prognostic Index (IPI) scores based on age-adjusted indices, and those who achieved at least a partial remission after five cycles of CHOP-based (CHOP or R-CHOP) , randomized to a total of six treatments of CHOP plus first-line autotransplantation, and another group treated with eight courses of CHOP, with second-line autotransplantation in patients who relapsed only [2]. First-line autotransplantation did not improve overall survival at two years (74% versus 71%). However, within the group’s analysis of 88 high-risk patients with IPI, autotransplantation yielded superior two-year disease-free survival (75% versus 41%) and overall survival (82% versus 64%). However, the data are small, and guidelines continue to withhold recommendation of first-line autotransplantation. An Italian trial had patients with an IPI score of intermediate-high or high receive R-CHOP every 14 days (122 patients; 8 cycles) or rituximab plus high-dose chemotherapy and autotransplantation (113 patients) [3]. At 5-year follow-up, there was no improvement in overall survival (74% versus 77%), as the rate of hematologic and infectious complications was higher in the high-dose chemotherapy group. In a similarly designed trial conducted by the German Study Group for Higher Non-Hodgkin’s Lymphoma (DSHNHL), first-line autologous transplantation did not show a benefit over aggressive conventional rituximab-based chemotherapy (CHOP plus etoposide 300 mg/m2 every two weeks) [4]. In another trial, 162 patients with aggressive B-cell lymphoma and high intermediate-risk or high-risk age-adjusted IPI scores were randomly assigned to R-CHOEP-14 or CHOEP plus autologous transplantation [4]. Severe (grade 3/4) hematologic and non-hematologic toxicities were more common in the latter. Overall survival (OS) was similar at a median follow-up of 42 months (74% vs. 70%). Therefore, the use of autologous transplantation in first remission is generally not advocated for most patients with DLBCL, including those with high intermediate-risk or high-risk IPI scores. Although a post hoc analysis of the S9704 intergroup trial suggests that autotransplantation is an option for patients with high-risk (rather than intermediate- to high-risk) IPI, given the uncertainty of this benefit, it would not outweigh the known complications associated with transplantation in most patients. More conclusions are awaited from new clinical trials.