Diffuse Aggressive Lymphoma

The aggressive non-Hodgkin’s lymphomas can be cured in more than half of the cases. However, there has been great variation in the results reported from individual clinical Phase II trials. This variation in result can be attributed to unrecognized heterogeneity in this group of diseases. Recent clinical and molecular studies have enabled us to define more homogenous population in which new therapies can be studied. For patients with advanced stages of diffuse large B cell lymphoma, a new standard of therapy exists. For patients with localized aggressive non-Hodgkin’s lymphomas, heterogeneity in patient selection prevents us from defining a new standard of care. Finally, in mantle cell lymphoma, new opportunities in drug discovery may permit advances in the treatment of this uniformly fatal malignancy. In Section I, Dr. Richard Fisher reviews the development of combination chemotherapy for patients with advanced stage diffuse large B cell lymphoma. Because of great heterogeneity in patients enrolled in Phase II studies, large randomized Phase III studies were required in the 1980s to define CHOP has the standard of care. This heterogeneity has now been defined carefully in the international prognostic factor index and more recently by gene array studies. It will now need to be incorporated prospectively into studies or retrospectively analyzed to understand clinical trial results. The addition of rituximab to CHOP has now been demonstrated to improve survival in two large Phase III studies in elderly patients. A recently presented study in younger patients suggests a similar benefit. Thus CHOP/rituximab has become the established standard of care for all patients with advanced stage diffuse large B cell lymphoma. Other concepts being evaluated to further improve on these results include: dose intensification; initial treatment with chemotherapy plus allogeneic stem cell transplantation; and infusional chemotherapy. Finally, the status of the treatment for relapsed patients will be defined.