The follicular non-Hodgkin's lymphomas--II. Prognostic factors: what do they mean?

The Ann Arbor staging classification has long been recognised to have shortcomings when used to stage the follicular lymphomas. To date, the identification of important prognostic variables has not succeeded in producing a superior staging classification that reflects the stages of dissemination of these processes in a way that can be used in the testing of new therapeutic strategies. A fresh look is taken at these factors. Data from 398 patients entered into the British National Lymphoma Investigation trials between 1974 and 1980, were analysed to evaluate the performance of the Ann Arbor staging classification. Multiple regression and proportional hazards techniques were used to determine what factors independently influence response to initial treatment, the durability of that response and ultimate survival, and to isolate factors that relate to disease progression from those that have other mechanisms of action. The Ann Arbor staging classification fared poorly, minimally separating relapse-free and cause-specific survival probabilities in patients with the largest staging groupings, III and IV. Significant prognostic heterogeneity was seen in both of these stage groupings, with 22% of patients with stage IV disease on the basis of marrow involvement having slightly better outcomes than patients with stage III disease. Significant differences in outcome were also observed between patients of different age and sex in each Ann Arbor stage grouping. Increasing number of lymph node regions involved, constitutional symptoms, the presence of splenomegaly and increasing age were observed to have powerfully independent adverse influence on probability of complete response to treatment and cause-specific survival. The evolution of the follicular lymphomas is reflected at the clinical level by an increase in the number of lymph node regions involved and splenomegaly. Simple classifications based on simple counts of lymph node regions involved and splenomegaly are more successful than the Ann Arbor staging classification in subdividing the series into patient subgroups that, regardless of gender or age, experience significantly different probabilities of responding completely to therapy and, as a consequence, relapse-free and cause-specific survival expectations. The definition of poor prognosis in subgroups may be of value in selecting patients for newer and more intensive therapeutic approaches.