Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma?

Abstract

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.