Salvage chemotherapy followed by high-dose therapy and autologous stem cell 
transplantation is the standard of treatment for chemosensitive relapses in 
diffuse large B-cell lymphoma. The addition of rituximab to chemotherapy has 
improved the response rate and failure-free survival after first-line treatment 
and relapses. Fewer relapses are expected, although there is no consensus on the 
best salvage regimen. The intergroup Collaborative Trial in Relapsed Aggressive 
Lymphoma (CORAL) set the limits for this standard of treatment after first 
comparing 2 salvage regimens: rituximab, ifosfamide, etoposide, and carboplatin 
(R-ICE) and rituximab, dexamethasone, aracytine, and cisplatin (R-DHAP). There 
was no difference in response rates or survivals between these salvage regimens. 
Several factors affected survival: prior treatment with rituximab, early relapse 
(< 12 months), and a secondary International Prognostic Index score of 2-3. For 
patients with 2 factors, the response rate to salvage was only 46%, which 
identified easily a group with poor outcome. Moreover, patients with an ABC 
subtype or c-MYC translocation responded poorly to treatment. More than 70% of 
patients will not benefit from standard salvage therapy, and continued progress 
is needed. Studies evaluating immunotherapy after transplantation, including 
allotransplantation, new conditioning regimens with radioimmunotherapy and other 
combinations of chemotherapy based on diffuse large B-cell lymphoma subtype, are 
discussed herein. Early relapses and/or patients refractory to upfront 
rituximab-based chemotherapy have a poor response rate and prognosis. A better 
biological understanding of these patients and new approaches are warranted.