Prognostic indicators in diffuse, aggressive non-Hodgkin's lymphomas: Regulators of growth fraction and programmed cell death

Less than half of patients with diffuse, aggressive non-Hodgkin's lymphoma are cured with conventional-dose chemotherapy. Prognostic indicators identifying those at greatest risk of treatment failure must be established so that novel therapeutic approaches may be studied in those patients most likely to benefit. To date, clinical features are the most powerful predictors of outcome, but are most likely surrogates for biologic characteristics. Individually, proliferative activity and regulators of programmed cell death have been identified as predictors of clinical outcome in the diffuse, aggressive non-Hodgkin's lymphomas. Recent studies suggest that proliferative and apoptotic pathways are closely interrelated. Prospective study of biologic correlates as part of large phase III clinical trials, especially those involving new agents such as the anti-CD20 monoclonal antibody, will help to determine whether treatment with biologic therapies is associated with different prognostic features than conventional chemotherapy. In addition, such studies will help to unravel the underlying biology of the lymphoid malignancies.