Prognostic significance of del 17p, ZAP-70 and CD38 as independent indicators for B-CLL: Correlation to response to treatment and disease outcome

Abstract

Prognostic markers as CD38 and ZAP-70 and specific chromosomal abnormalities as del 17p have now been developed to refine the risk of progressive disease in chronic lymphocytic leukemia (CLL). This study analyzed 40 recently diagnosed, untreated B-CLL patients for CD38 and ZAP-70 expression by flow cytometry and for del 17p by conventional cytogenetics (CCG) and by fluorescence in situ hybridization (FISH) technique to evaluate their effect on the clinical course of CLL and as risk factors for disease progression in addition to their impact on response to treatment and disease outcome. Twenty healthy age- and sex-matched subjects were included as a control. The results revealed that CD38 and ZAP-70 expression were detected in 42.5% and 47.5% of cases, respectively. They were associated with an unfavorable clinical course. Higher levels were significantly associated with increased risk of unfavorable response to treatment (P = 0.003), with poor clinical outcome (P = 0.0001). Del 17p was detected in 35% of cases by FISH technique and in 7.5% by CCG. The deletion was significantly associated with progressive clinical course; poor response to treatment (P = 0.007) but not with disease outcome (P = 0.103). Combined analysis of ZAP-70 and CD38 yielded concordantly negative results in 50% of patients and concordantly positive results in 40% of patients, while 10% were discordant. CD38⁺/ZAP-70⁺ patients were significantly associated with progressive disease (P < 0.05) and with del 17p than CD38^-/ZAP-70^- patients (P = 0.008). Time to disease progression (TDP) was 6 months among CD38⁺/ZAP-70⁺ patients as compared to 16 months in CD38^-/ZAP-70^- patients. In patients with discordant results, the TDP was 9 months. Over-representation of the three parameters (CD38, ZAP-70 and del 17p) was detected in 22.5% of cases, and pointed towards even shorter TDP (4.5 months), more aggressive disease; more resistance to chemotherapy and poor outcome thus providing a precise tool for identifying high-risk patients. In conclusion, the combined expression of CD38 and ZAP-70 together with del 17p in CLL is a precise diagnostic tool for identifying high-risk patients and convey rapid progression; they are accurate predictors of clinical outcome thus could be used to indicate when more novel chemotherapeutic approaches are needed and provided help in guiding individual patient treatment.

Keywords: CLL; CD38; ZAP-70; Del 17p; Immunophenotyping; FISH; Survival study