252 American Society of Hematology Diffuse Large B-Cell Lymphoma: Risk Stratification and Management of Relapsed Disease

The clinical factors described by the International Prognostic Index (IPI) provide a model for risk stratifi-cation in diffuse large B-cell lymphomas (DLBCLs). However, there is variability in outcome within IPI risk groups, indicating the biological and clinical heteroge-neity of these diseases. Studies of gene expression profiling (GEP) in DLBCL are uncovering biological heterogeneity with prognostic significance. Various gene expression signatures with predictive value independent of the IPI are now recognized. Immuno-phenotypic features of DLBCL have also been shown to have prognostic value. The use of fluorodeoxy-glucose–positron emission tomography (FDG-PET) scanning may provide additional predictive informa-tion when used at diagnosis or soon after initiation of treatment. Future prognostic models in DLBCL are likely to incorporate functional imaging, immuno-phenotype and GEPs as well as clinical data in risk stratification and choice of treatment. Treatment of relapsed DLBCL remains a major problem. High-dose therapy (HDT) and stem cell transplantation (SCT) has been shown to produce superior overall survival (OS) compared with conven-tional dose salvage therapy in patients with relapsed, chemosensitive DLBCL. However, only 20 % to 30 % of patients are cured by this approach, and the effective-ness of HDT and SCT in patients treated with ritux-imab-based combinations as first-line therapy is unknown. Although new transplant techniques includ-ing non-myeloablative allogeneic SCT are being investigated, their role is unclear. New treatment strategies are needed for these patients. The use of molecular techniques such as GEP is identifying many potential new therapeutic targets in DLBCL including histone deacetylase, HLA-DR, bcl-2, bcl-6, mTOR an