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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Monoclonal antibodies in the management of acute leukemia
J C Wang1, P Beauregard, P Soamboonsrup
1Department of Laboratory Medicine, Hamilton Civic Hospitals, Ontario, Canada.
This report reviews the diagnostic significance of immune markers, their relationship to patient outcome, and the therapeutic uses of monoclonal antibodies (MoAbs) in acute leukemia. Immunophenotyping allows for rapid and reproducible diagnosis in the majority of cases of acute leukemia. It is of particular importance in recognizing the major immunologic subclasses of acute lymphoblastic leukemia (ALL), and in identifying subtypes of acute myeloblastic leukemia (AML) which cannot be differentiated by morphology and cytochemistry alone, such as FAB M0 or M7. Immune marker analysis has been used to detect minimal residual disease in patients' bone marrow and CSF after treatment. However, the presence of leukemia-associated phenotypes on small numbers of normal cells may reduce the sensitivity of detection in some cases. The prognostic value of immune markers in AML is limited. In ALL, the prognostic significance of the different immunophenotypic subtypes has been lessened by modern treatment protocols. The relationship of mixed-lineage or biphenotypic antigen expression to patient outcome in both AML and ALL is unclear. Therapeutic applications of MoAbs in acute leukemia include immunologic techniques for purging malignant cells from autografts prior to transplantation, T-lymphocyte depletion from allografts as a strategy to reduce graft-versus-host disease, and the use of flow cytometry to monitor the timing and extent of leukapheresis in peripheral stem cell transplantation. MoAbs have also enabled the recent development of transplantation protocols using positively-selected CD34+ stem cells.
This report reviews the diagnostic significance of immune markers, their relationship to patient outcome, and the therapeutic uses of monoclonal antibodies (MoAbs) in acute leukemia. Immunophenotyping allows for rapid and reproducible diagnosis in the majority of cases of acute leukemia. It is of particular importance in recognizing the major immunologic subclasses of acute lymphoblastic leukemia (ALL), and in identifying subtypes of acute myeloblastic leukemia (AML) which cannot be differentiated by morphology and cytochemistry alone, such as FAB M0 or M7. Immune marker analysis has been used to detect minimal residual disease in patients' bone marrow and CSF after treatment. However, the presence of leukemia-associated phenotypes on small numbers of normal cells may reduce the sensitivity of detection in some cases. The prognostic value of immune markers in AML is limited. In ALL, the prognostic significance of the different immunophenotypic subtypes has been lessened by modern treatment protocols. The relationship of mixed-lineage or biphenotypic antigen expression to patient outcome in both AML and ALL is unclear. Therapeutic applications of MoAbs in acute leukemia include immunologic techniques for purging malignant cells from autografts prior to transplantation, T-lymphocyte depletion from allografts as a strategy to reduce graft-versus-host disease, and the use of flow cytometry to monitor the timing and extent of leukapheresis in peripheral stem cell transplantation. MoAbs have also enabled the recent development of transplantation protocols using positively-selected CD34+ stem cells.
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