الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 110 |  |  |
| | | from | 110 | | |
Abstract
CLL is the most common leukemia in Western countries, representing approximately 40% of all leukemias worldwide.
CLL is defined by the presence of at least 5×109/l monoclonal B lymphocytes in the peripheral blood persisting for >3 months with the characteristic CLL immunophenotype.
Expression of CD38 and ZAP-70 is a predictor for an unfavourable outcome in terms of TFI.
Prognostication in CLL is an active research field and many studies tried to define not only prognostic markers able to predict the clinical course at diagnosis, but also predictive markers able to predict response to treatment.
Regulatory T cells (Tregs) are defined as CD4+ T-cells expressing CD25 at high levels, cytoplasmic FoxP3, and very low to no CD127 on their surface. Treg cells are able to suppress immune responses by direct interaction with other immune cell types or through immunosuppressive cytokines; they appear crucial in maintaining immune homeostasis, mediating peripheral tolerance and preventing autoimmunity.
Several reports have been published about the elevated number of Treg cells in the peripheral blood of patients with solid tumors and hematologic malignancies as well, but the mechanisms driving Tregs expansion in cancer are not fully understood. Also an increased number of Treg cells in peripheral blood of patients with CLL has been reported by several authors in the last recent years.
The aim of the present work was to evaluate the expression of regulatory T cells in CLL patients and to correlate it with different Patients’ characteristics.
The present study was conducted on 30 newly diagnosed CLL patients admitted to Alexandria Main University Hospital during the period from September 2015 to October 2016.The patient group included 20 males and 10 females and their age ranged between 45-93 years. Patients were classified according to modified Rai and Binet staging system. Twenty age and sex matched healthy individuals were included as a control group.
All patients in the study were subjected to full history taking, complete clinical examination with special emphasis on organomegaly and lymphadenopathy. The patients were diagnosed by flow cytometric immunophenotyping according to CLL scoring system. CD38 and ZAP-70 expression was done by flow cytometry and LDH level was measured for all patients. Peripheral blood Treg cells were evaluated in CLL patients and controls by multi-color Flow cytometry using their specific panel of MoAbs: CD4, CD25 and FoxP3.
In our study we found that the CLL patients had a significantly higher absolute CD4+ T cell count than the control group; although the relative CD4+ cell count was lower in CLL patients than the control group. The absolute Tregs count was also significantly higher in CLL patients than controls although the Treg percentage was slightly lower in CLL patients than the control group. No significant relation was found between the absolute counts of Tregs cells in the peripheral blood of CLL patients and neither the age nor sex.
There was a significant difference of the mean absolute Tregs count between patients with hemoglobin more than 10g/dl and those with hemoglobin less than 10g/dl, with a higher absolute Treg cell count associated with hemoglobin less than 10g/dl. Similarly Tregs count was significantly higher in patients with platelets counts <100×109/L than in those with higher platelet counts. A significant positive correlation was found between absolute Tregs count and both the total leucocytic count and the absolute lymphocytic count.
Tregs count was also higher in patients with high LDH level than patients with normal LDH but the difference didn’t reach a statistically significant level.
A progressive increase in Tregs count was found with disease progression with the highest numbers of Tregs found in patients with advanced stage [High risk (modified Rai) /Rai III – IV/ Binet stage C], followed by patients with [Intermediate risk (modified Rai) / Rai I – II/ Binet stage B] and with lowest numbers in [low risk (modified Rai) / Rai stage 0/ Binet stage A]. The relation between peripheral blood Treg count and CD38, ZAP-70 could not be studied because of the very small number of the CD38 and ZAP-70 positive cases.