Diffuse large B-cell lymphoma

First-line treatment for patients with DLBCL is based on the individual IPI score and age, and three major subgroups should be considered: elderly patients (>60 years, aaIPI = 0-3); young patients with low risk (<60 years, aaIPI = 0-1); young patients with high risk (<60 years, aaIPI = 2-3). The combination of the anti-CD20 monoclonal antibody rituximab and CHOP chemotherapy, every 14 or 21 days, is the standard treatment for DLBCL patients. Recent randomized trials suggest that high-dose chemotherapy supported by autologous stem cell transplant (HDC/ASCT) should not be used as upfront treatment for young high-risk patients outside prospective clinical trials. HDC/ASCT is actually recommended in young patients who did not achieve CR after first-line chemotherapy. Consolidation radiotherapy should be reserved to patients with bulky disease who did not achieve CR after immunochemotherapy. Patients with high IPI score, which indicates increased LDH serum level and the involvement of more than one extranodal site, and patients with involvement of certain extranodal sites (a.e., testes and orbit) should receive CNS prophylaxis as part of first-line treatment. HDC/ASCT should be considered the standard therapy for DLBCL patients with chemotherapy-sensitive relapse. Overall results in patients who cannot be managed with HDC/ASCT due to age or comorbidity are disappointing. New effective and less toxic chemotherapy drugs or biological agents are also worth considering for this specific and broad group of patients. Several novel agents are undergoing evaluation in DLBCL; among other, immunomodulating agents (lenalidomide), m-TOR inhibitors (temsirolimus and everolimus), proteasome inhibitors (bortezomib), histone deacetylase inhibitors (vorinostat), and anti-angiogenetic agents (bevacizumab) are being investigated in prospective trials.