| Abstract [eng] |
The investigations presented in this dissertation were initiated with the intention to evaluate the prognostic value of plasma cells immunophenotypic analysis in multiple myeloma patients. We tested the hypothesis that kinetics of peripheral blood circulating plasma cells in response to first chemotherapy cycle could identify patients refractory to given treatment. We employed novel original methodology for plasma cells immunophenotyping: cells were stained in two tubes with antibody combinations CD56/CD138/CD45/CD19/CD38/CD20 and cLambda/cKappa/CD138/CD19/CD38/CD56. We found that ~30% of all plasma cells in bone marrow of healthy donors are immunophenotypically aberrant by CD56 and/or CD19 marker expression. We optimized immunophenotypic differentiation between malignant and normal plasma cells. Non reduction of malignant circulating plasma cells in response to first chemotherapy cycle predicted early progression with sensitivity and specificity of 91.7% and 93.3%, respectively. Time to progression and overall survival were significantly shorter in these patients as compared to patients with undetectable or reduced malignant circulating plasma cells. We also evaluated the clinical value of normal plasma cell subpopulation detection in peripheral blood and bone marrow of multiple myeloma patients. In summary, we demonstrated that immunophenotyping of plasma cells using multiparameter flow cytometry provides important prognostic information. The major finding was that the kinetics of malignant circulating plasma cells in response to first chemotherapy cycle could identify patients, refractory to given therapy who are at risk for early progression, more precisely than a standart response criteria. |
