Clinical Staging and Flowcytomteric CD38 and Zap 70 Prognostic Indicators in Sudanese Patients with Chronic Lymphocytic Leukemia


Background: The clinical course of chronic lymphocytic leukemia is highly variable. The determination of ZAP70 and CD38 is increasingly utilized as prognostic factor for chronic lymphocytic leukemia. The aim of conducting this study was to investigate the frequency of CD38 and ZAP70 expression among Sudanese Chronic lymphocytic leukemia (CLL) patients and to relate them to the Binet and Rai clinical staging systems.

Method: A total of 93 patients (mean age; 62.29 ± 11.68, sd) were enrolled in this cross-sectional study. CD38 and ZAP70 expression levels were measured with four color flowcytometry using the cut-off values of 20% for ZAP70 and 30% for CD38 expression. Staging was assessed by using clinical examination and CBC for all patients. Data were analyzed using the Statistical Package for Social science for Windows (SPSS), version 22.

Results: There were 93 CLL patients and the median age of the group was 63 years (36–95 years). About 71% of the patients presented with lymphadenopathy, 53.8% with splenomegaly, 73.1% with anemia, and 45.2% with thrombocytopenia. There was higher frequency of Binet stage C and Rai stage IV (62 [66.6%] patients and 34 [36.5%] patients, respectively). In addition, CD38 and ZAP70 showed higher frequency among Binet and Rai advance stages. ZAP70 and CD38 positivity were detected in 21 patients (22.6%) and 31 patients (33.3%), respectively. There was no statistically significant association between ZAP70 and CD38 and clinical staging systems (P-value > 0.05).

Conclusion: No significant association was observed between Flowcytometric (CD38 and Zap70) Prognostic Indicators and clinical staging systems.

Keywords: chronic lymphocytic Leukemia, Flowcytometry, ZAP70, CD38, clinical staging systems

[1] Rozman, C. and Montserrat, E. (1995). Chronic lymphocytic leukaemia. N Engl J Med, vol. 333, pp. 1052–1057.

[2] Binet, J. L., Auquier, A., Dighiero, G., et al. (1981). A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer, vol. 48, pp. 198–206.

[3] Rai, K. R., Sawitsky, A., Cronkite, E. P., et al. (1975). Clinical staging of chronic lymphocytic leukemia. Blood, vol. 46, no. 2, pp. 219–234.

[4] Schroers, R., Griesinger, F., Tru¨mper, L., et al. (2005). Combined analysis of ZAP-70 and CD38 expression as a predictor of disease progression in B-cell chronic lymphocytic leukemia. Leukemia, vol. 19, no. 5, pp. 750–758

[5] Rosenwald, A., Alizadeh, A. A., Widhopf, G., et al. (2001). Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med, vol. 194, no. 11, pp. 1639–1647.

[6] Wiestner, A., Rosenwald, A., Barry, T. S., et al. (2003). ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood, vol. 101, no. 12, pp. 4944–4951.

[7] Chen, L., Widhopf, G., Huynh, L., et al. (2002). Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia. Blood, vol. 100, no. 13, pp. 4609–4614.

[8] Chen, L., Apgar, J., Huynh, L., et al. (2005). ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia. Blood, vol. 105, no. 5, pp. 2036–2041.

[9] Crespo, M., Bosch, F., Villamor, N., et al. (2003). ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med, vol. 348, no. 18, pp. 1764–1775.

[10] Orchard, J. A., Ibbotson, R. E., Davis, Z., et al. (2004). ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet, vol. 363, no. 9403, pp. 105–111.

[11] Rassenti, L. Z., Huynh, L., Toy, T. L., et al. (2004). ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med, vol. 351, no. 19, pp. 893–901.

[12] Du¨rig, J., Nu¨ckel, H., Cremer, M., et al. (2003). ZAP-70 expression is a prognostic factor in chronic lymphocytic leukemia. Leukemia, vol. 17, no. 12, pp. 2426–2434.

[13] Schroers, R., Pukrop, T., Du¨rig, J., et al. (2004). B-cell chronic lymphocytic leukemia with aberrant CD8 expression: genetic and immunophenotypic analysis of prognostic factors. Leukemia & Lymphoma, vol. 45, no. 8, pp. 1677–1681.

[14] Deaglio, S., Capobianco, A., Bergui, L., et al. (2003). CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells. Blood, vol. 102, no. 6, pp. 2146–2155.

[15] Damle, R. N., Wasil, T., Fais, F., et al. (1999). Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood, vol. 94, no. 6, pp. 1840–1847.

[16] Hamblin, T. J., Orchard, J. A., Ibbotson, R. E., et al. (2002). CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease. Blood, vol. 99, no. 3, pp. 1023–1029.

[17] Cheson, B. D., Bennett, J. M., Grever, M., et al. (1996). National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood, vol. 87, no. 12, pp. 4990–4997.

[18] Hallek, M., Cheson, B. D., Catovsky, D., et al. (2008). Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood, vol. 111, no. 12, pp. 5446–5456.

[19] Matutes, E., Owusu-Ankomah, K., Morilla, R., et al. (1994). The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia, vol. 8, no. 10, pp. 1640–1645.

[20] Moreau, E. J., Matutes, E. A., 'Hern, R. P., et al. (1997). Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b). Am J Clin Pathol, vol. 108, no. 4, pp. 378–382.

[21] Vroblová, V., Smolej, L., Vrbacky, F., et al. (2009). Biological prognostic markers in chronic lymphocytic leukemia. Acta Medica, vol. 52, no. 1, pp. 3–8.

[22] Del Poeta, G., Maurillo, L., Venditti, A., et al. (2001). Clinical significance of CD 38 expression in chronic lymphocytic leukemia. Blood, vol. 98, no. 9, pp. 2633–2639.

[23] Gogia, A., Sharma, A., Raina, V., et al. (2013). Prevalence of ZAP-70 and CD 38 in Indian chronic lymphocytic leukemia patients. Indian Journal of Cancer, vol. 50, no. 4, pp. 333–336.

[24] Hus, I., Podhorecka, M., Bojarska-Junak, A., et al. (2006). The clinical significance of ZAP70 and CD 38 expression in B cell chronic lymphocytic leukemia. Ann Oncol, vol. 17, no. 4, pp. 683–690.

[25] D'Arena, G., Tarnani, M., Rumi, C., et al. (2007). Prognositc significance of combined analysis of ZAP 70 and CD 38 in chronic lymphocytic leukemia. Am J Haematol, vol. 82, no. 9, pp. 787–791.

[26] Zenz, T., Frohling, S., Mertens, D., et al. (2010). Moving from prognostic to predictive factors in chronic lymphocytic leukaemia (CLL). Best Pract Res Clin Haematol, vol. 23, no. 1, pp. 71–84.