Natural history of stage A chronic lymphocytic leukaemia untreated patients

S ummary . In chronic lymphocytic leukaemia (CLL), stage A was defined in 1979 as the best prognostic group of the three‐stage (A, B, C) classification which was thereafter adopted by an International Workshop on CLL. Recently, the question of whether or not all stage A patients should be treated was raised by authors who described potential harmful effects of treatment among stage A patients and heterogeneity of stage A with respect to survival and disease progression. In this work, we studied the natural history of stage A‐CLL in order to determine on which grounds a decision to treat should be made. We performed a prognostic study on 309 untreated stage A‐CLL patients enrolled in a randomized clinical trial from 1980 to 1985. Our aim was to segregate a subgroup with a low probability of disease progression and death. We used three endpoints: overall survival (50 deaths), disease progression to stage B or C (78 events) and disease progression to stage C (39 events). Multivariate analyses, using Cox's model, selected nine variables as having a prognostic value for at least one endpoint, namely age, sex, general symptoms, involved axillary lymph node, splenomegaly, haemoglobin, platelets, lymphocyte count and bone‐marrow infiltration. By considering the three endpoints jointly, we obtained a proposed definition of smouldering CLL based on four variables, namely haemoglobin level, lymphocyte count, the number of enlarged areas and bone‐marrow infiltration. However, we did not succeed in better defining smouldering CLL than in a previous proposal, based on haemoglobin level and lymphocyte count. Moreover, whatever the definition used, including other previous works, disease progression within 5 years was still observed for about 10% of patients with smouldering CLL. Future attempts to define smouldering CLL could perhaps benefit from using biological markers.