[CD5-positive DLBCL: molecular basis and treatment strategies]

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) comprises 10% of DLBCL and is one of the immunohistochemical subgroups in the 2008 WHO classification. It shows many distinct clinical characteristics including elderly onset, advanced stage at diagnosis, high serum lactate dehydrogenase level and frequent involvement of extranodal sites. CD5+ DLBCL has a poor prognosis and a relatively high incidence of central nervous system (CNS) relapse even in the rituximab era. Eighty-three percent of patients who experienced CNS relapse had brain parenchymal disease. Immunohistochemically, 82% of CD5+ DLBCLs are classified as the non-germinal center B-cell type. BCL2 protein is positive in more than 70% of patients. P-glycoprotein, which is associated with multidrug resistance, was positive in 59% of patients with CD5+ DLBCL tested at Mie University Hospital. Based on gene expression profiling, most patients with CD5+ DLBCL are classified as activated B-cell-like (ABC) DLBCL. A more effective first-line therapy for CD5+ DLBCL needs to be explored. In Mie University Hospital, four patients with newly diagnosed stage IV CD5+ DLBCL were successfully treated with dose-adjusted (DA)-EPOCH-R combined with hi-dose methotrexate (HD-MTX). Based on these observations, a phase II study of DA-EPOCH-R/HD-MTX for newly diagnosed CD5+ DLBCL (PEARL5 trial) is ongoing in Japan.