Prognostic significance of combined analysis of ZAP-70 and CD38 in chronic lymphocytic leukemia

The clinical heterogeneity that characterizes chronic lymphocytic leukemia (CLL) poses critical questions concerning the identification of high risk patients. Unmutated IgV_H genes, CD38 and ZAP-70 expression have emerged as the most useful tools in identifying aggressive CLL. The simultaneous expression of ZAP-70 and CD38 in 157 patients with CLL has been evaluated. Fifty-seven patients (36%) were positive for ZAP-70 and 46 patients (29%) were positive for CD38. Both molecules were highly correlated and predictive of the clinical course of the disease. According to the simultaneous evaluation of ZAP-70 and CD38, patients were divided into three groups. In 81 patients (52%), there was a negative concordance of both molecules (ZAP-70^-/CD38 ^-); in 27 patients (17%) there was a positive concordance (ZAP-70⁺/CD38⁺); in 49 patients (31%) there was a discordant expression (ZAP-70⁺/CD38^- and ZAP-70 ^-/CD38⁺). A comparison of the clinical and laboratory data showed in ZAP-70⁺/CD38⁺ patients a significantly higher bone marrow and peripheral blood lymphocytosis, lower hemoglobin levels, more advanced clinical stage, and higher number of unmutated IgV_H status with respect to the other two groups. Furthermore, ZAP-70⁺/CD38 ⁺ patients displayed a much shorter treatment-free interval (median 12 months vs 42 months in discordant patients and not reached in ZAP-70 ^-CD38^- patients). These results prove that the concomitant evaluation of ZAP-70 and CD38 expression allows the separation of CLL patients in prognostic subgroups and suggest that their simultaneous assessment should become an integral component of the CLL diagnostic grid.