Relative Value of CD38 and ZAP-70 Versus Immunoglobulin Mutation Status in Predicting Early Disease Progression in Chronic Lymphocytic Leukemia.

We assessed the relative value of CD38 in predicting the need for early treatment in 307 patients with chronic lymphocytic leukemia (CLL) previously characterized for ZAP-70 and immunoglobulin heavy-chain-variable region gene (IgVH) mutational status (

We explored the TTT based only on flow cytometric parameters (CD38 and ZAP-70) and investigated whether addition of mutation status significantly altered our predictions. For most patients, the knowledge of CD38 and ZAP-70 provided a reliable means for predicting the TTT and the knowledge of the IgVH mutation status did not substantially alter the prediction. Only in 41 cases (14% of the total), where the CLL cells were CD38+ but negative for ZAP-70, was the prediction significantly improved by inclusion of IgVH mutation status. The median TTT of this group of 41 patients was 7.8 years. Addition of mutation status identified a subgroup of 20 patients with unmutated IgVH genes for whom median TTT was estimated at 4.6 years; 21 patients with mutated IgVH genes had a median TTT of 8.4 years. For patients with CLL cells that were CD38-negative and either negative or positive ZAP-70, stratification via IgVH mutation status did not identify subgroups within each of these categories that had significantly different median TTT. We conclude that knowledge of CD38 and ZAP-70, as assessed by the CRC, can reliably predict TTT in most patients with CLL. For the 14% of cases that are CD38+ but negative for ZAP-70, determining the IgVH mutation status may provide added value in predicting the time from diagnosis to initial therapy.