ZAP-70 Versus CD38 Expression as the Prognostic Factors in B-Cell Chronic Lymphocytic Leukemia.

B-CLL is a heterogeneous disease with a highly variable clinical course. The mutational status of immunoglobulin heavy-chain variable region (IgVH) genes in the leukemic cells seems to be of great importance in assessing the prognosis in B-CLL. Recent studies have shown that both CD38 and ZAP-70 might be surrogate markers for IgVH mutation identifying patients with a more aggressive clinical course. The aim of our study was to estimate the clinical value of both ZAP-70 and CD38 as B-CLL prognostic factors.

The analysis with use of flow cytometry technique was performed at diagnosis in the group of 100 B-CLL patients. 39/100 persons were defined as ZAP-70 positive and 61/100 persons as ZAP-70 negative (based on 20% cut off value in the CD19+/CD5+ population). ZAP-70+ patients had significantly higher lymphocytosis (p=0.003) and LDH level (p=0.009), while hemoglobin (p=0.049) and platelet levels (p=0.002) were significantly lower than in ZAP-70− patients. The proportion of CD19+/CD5+ cells expressing ZAP-70 correlated significantly with stage of disease (p=0.035). Patients with Rai stage III–IV (32/100 patients) had higher percentage of CD19+/CD5+/ZAP-70+ cells than patients with stage 0-II (68/100 patients) (24.81±17.40% and 14.89±13.54%, respectively, p=0.008). The mean treatment-free interval was longer in the ZAP-70 negative (8.46±4.63 months) than in the ZAP-70 positive patients (1.16±0.28 months). Furthermore, patients requiring treatment (57/100) had significantly higher percentage of CD19+/CD5+ cells expressing ZAP-70 protein than untreated patients (20.18±15.09 and 13.44±11.84, respectively, p=0.034). In the midst of patients requiring treatment, percentage of CD19+/CD5+/ZAP-70+ cells was significantly lower in patients achieving remission after first line therapy (26/57) than in patients with progressive disease (31/57) (p=0.004).

According to CD38 analysis the patients with ≥ 20% of CD38 expression were considered positive (CD38+) and those < 20% were considered negative (CD38−). Patients CD38 positive, like the ZAP-70 positive patients, had more advanced Rai stage of disease, significantly higher lymphocytosis and LDH serum level. Patients requiring treatment had higher percentage of CD19+/CD5+CD38+ cells than untreated patients, however no statistical significance was detected. Percentage of CD19+/CD5+CD38+ was not a dicriminating factor between patients with good response to the first line therapy and those with progressive disease.

The obtained results indicate that both ZAP-70 and CD38 expression may be prognostic markers identifying a subgroup of B-CLL patients with aggressive clinical presentation. However, the ZAP-70 expression seems to have more prognostic power, especially in predicting response to the first line therapy.