New proposal for the treatment of poor prognosis young patients with advanced stage diffuse large B-cell lymphoma

Patients with DLBCL now have a better outcome with a longer survival because of two major developments: 1) increasing the dose of active drugs with shortening the time between cycles, resulting in dose-dense or dose-intense regimens; and 2) combining rituximab with chemotherapy. Both strategies were associated with a better clinical outcome, particularly in patients without adverse prognostic factors. Poor risk patients in the age range of 60 to 65 years may benefit from a combination of dose-dense or dose-intense regimens plus rituximab. Young patients with poor risk DLBCL defined by an aaIPI of 2 or 3 and age younger than 60 years, are characterized by truly refractory disease, evidenced by progression during or early after treatment, or later relapse. Attempts to modify treatment including immunotherapy to improve the response rate and reduce the proportion of patients with progressive disease have been only partially successful: to date: the best progression-free survival was 51%. In contrast, some attempts to decrease the high resistant and relapse rate with sequential high-dose chemotherapy with rituximab (R-HDS) and autologous stem cell transplantation (ASCT) have succeeded. On the basis of these promising results, GITIL launched a prospective phase III randomized trial comparing the efficacy and safety of dose-dense CHOP plus rituximab with R-HDS and ASCT. Preliminary data show that intensive programs such as dose-dense chemo-immunotherapy and R-HDS with ASCT are feasible until 65 years with a manageable toxic profile, also on multi-centre basis.