Complex Immunophenotypic Changes as Prognosis Panel in Chronic Lymphocytic Leukemia

Abstract

Brief Abstract The present study proposes to asses the prognosis with consecrated markers CD38 and the new ZAP-70 related to the various patterns of CLL complex immunophenotype: cyclin D1, CD38, CD20, FMC7, CD23. This particular combination could be used as a prognosis panel in CLL. Brief Abstract Background Chronic lymphocytic leukemia (CLL) has many other prognostic markers established in the past years related to disease and to the patient status, and the most important seem to now be immunophenotypical, genetic, and molecular. CD38 and ZAP-70 are now used in a strong prognosis panel of markers for CLL. Aims The present study proposes to assess the prognosis with consecrated markers CD38 and the new ZAP-70 related to the various patterns of CLL immunophenotype. Patients and Methods We have analyzed 187 patients diagnosed with CLL in order to find correlations between clinical stage, immunophenotype, and outcome. Results We found correlations between expression of CD38 related to clinical outcome, (dr: 0.541; P P = .018). The expression of BCL-2 was correlated to outcome (dr: 0.533; P P P = .014) and BCL-2 expression ( P = .034). Lower expression CD23 was associated with poor outcome and expression of CD38 and ZAP-70 ( P value + (28% vs. 3%), FMC7 + (33% vs. 8%), and lower CD23 (30%-60% vs. > 60%). Also, CD38 was positive in 44% vs. 10% and ZAP-70 in 66% versus 5%. This association defines a lymphoma-like immunophenotype for cyclin D1—positive cases. Treatment was chlorambucil, fludarabine/cyclophosphamide (FC), or FC + rituximab (FCR). Conclusion Flow cytometry is the most practical method used in CLL for diagnosis and prognosis evaluation. The immunophenotypical markers surrogate for IgVH mutation status, as CD38 and ZAP-70 have a strong correlation with outcome in CLL, and our results found that analysis by flow cytometry of both CD38 and ZAP-70 could be used in the evaluation of patients with CLL as strong prognosis markers. The complex immunophenotype in CLL could be used to define 2 main prognosis patterns: (1) cyclin D1—positive, CD38 positive, CD20 high, FMC7 positive, CD23 weak with poor prognosis; and (2) cyclin D1—negative, CD38 negative, CD20 low, FMC7 negative, CD23 high with good prognosis. These patterns have strong association with expression of ZAP-70 and could be used as prognosis assessment of patients with CLL.