Timing of diagnosis and lymphocyte accumulation patterns in chronic lymphocytic leukemia: Analysis of their clinical significance

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Abstract
In order to evaluate the clinical significance of the timing of diagnosis in chronic lymphocytic leukemia (CLL), we studied the diagnostic latency (DL), a variable related both to lymphocyte count and to lymphocyte doubling time (LDT), which points out the interval between the date of CLL diagnosis and the time at which it could have been made (lymphocyte count in peripheral blood of at least 5.0 .times. 109/l). In two different series accounting for 221 previously untreated CLL patients the trends of the DL tended to decrease as the risk increased. In other words, the more advanced the clinical stage the shorter the DL. On the other hand, the values of lymphocyte accumulation rate (LAR), which defines the speed at which the number of lymphocytes increases over the time, were significantly lower in earlier stages of disease. Both DL and LAR had a significant impact on survival when investigated by means of univariate analysis. In a Cox''s regression analysis applied to a training set of 122 patients, the combination of international clinical stages, LAR and age had the strongest value in predicting survival. The resulting model was validated in an independent subset of 99 patients (test-set cases) leading to a classification of patients into low-, intermediate-, and high-risk groups with 5-year survival rates of 89%, 31% and 8%, respectively, and with distinctively different annual mortality rates (p < 0.001). Finally, when multivariate analysis was applied to study disease progression, LAR was the first variable to enter the regression model (p = 0.0001).