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Abstract
Chronic lymphocytic leukemia is a lymphoproliferative disorder characterized by the monoclonal expansion of B lymphocytes in the peripheral blood, bone marrow, and lymphoid organ. It is the most common leukemia in adults in Western countries, accounting for approximately 25% to 30% of all leukemias.
The disease presents a heterogeneous clinical course, with some patients surviving for many years without requiring any specific therapy and others progressing despite aggressive treatment, this made CLL a major interest for a lot of researchers who try to find answers about unsolved issues like the origin of the disease, possible causative stimuli and their effect on the outcome of the disease and response to treament.
After decades of conservative approach, the overall management of patients with CLL has changed considerably over the last years on the basis of improvement in the understanding of the biologic properties of the disease.
In the present study, we tried to highlight a particular aspect of CLL which is the monoclonal nature of this disease, the aim was the application of immunofixation technique and monoclonal light chain detection by nephelometry to study the pattern of monoclonality in cases diagnosed as CLL.
In immunofixation technique, monoclonal protein is characterized by the presence of a sharp, well-defined band with a single heavy chain and a similar band with a kappa or lambda light chain, while polyclonal gammopathy is characterized by a broad diffuse band with one or more heavy chains and kappa and lambda light chains. In nephelometry, monoclonality is detected through analyzing the κ /λ ratio by quantitative assays for kappa (κ) and lambda (λ) light chains (the typical κ /λ ratio is ~2), monoclonal light chain elevation is defined as elevated either of the light chains with an abnormal light chain ratio while polyclonal light chain elevation is defined as elevated both light chains with a normal light chain ratio.
The present study was conducted on 30 B-CLL patients. The initial diagnosis was based on clinical features, absolute lymphocytosis >5×109/ L, morphology of the PB and immunophenotyping of the lymphoid cells.
The present work results revealed that no monoclonal band was detected by immunofixation technique, instead ,the polyclonal pattern was observed. On the other hand, we were able to prove the presence of monoclonal protein in the sera of CLL patients by quantification of κ/λ ratio and its incidence was 10%. The monoclonal typing by this method came in agreement with the surface immunoglobulin light chain detected on tumor cells by flowcytometry, nevertheless, there was no correlation between either of light chains κ , λ and absolute lymphocyte count in these cases ( P = 0.732 , 0.743 respectively) . Also the measurements of light chains κ , λ did not correlate with neither age (P = 0.160 , 0.349) nor clinical stage of the disease (P = 0.836 , 0.499 respectively).
Additionally we found that the overall abnormalities in light chains were 60%, 10%(3/30) presented a monoclonal elevation, , 13.3%(4/30) presented a polyclonal elevation, 26.7%(8/30) showed decrease in both light chain denoting bone marrow suppression, 3.3% (1/30) had elevated λ and low borderline κ / λ that may be an early stage of monoclonality and finally 6.6 (2/30) showed decrease in one of the light chains .
We concluded that monoclonal immunoglobulins do present in the sera of CLL patients proved by using nephelometric light chain measurement. This technique is rather simple quantitative test for detection of monoclonality and may provide information about the disease progression if integrated in the routine work up of CLL patients. Also immunofixation electrophoresis is not a sensitive technique in detection of monoclonality in CLL patients and it should be restricted to cases that give initial impression of monoclonality by protein electrophoresis.