Diagnostic and Prognostic Value of MFC
. van de Loosdrecht A. 05/19/11; 7626
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1; describe the role of flow cytometry in the prognostication of MDS
2; describe the role of flow cytometry in the prediction of response to standard growth factor treatment (Epo/G-CSF} in lower risk MDS
3; to describe some flow cytometric parameters which are of importance in flow cytometry
4; to describe current pitfalls of the flow cytometric method in MDS
2; describe the role of flow cytometry in the prediction of response to standard growth factor treatment (Epo/G-CSF} in lower risk MDS
3; to describe some flow cytometric parameters which are of importance in flow cytometry
4; to describe current pitfalls of the flow cytometric method in MDS
Flow cytometry in myelodysplastic syndromes. Definitions, Clinical and Diagnostic Applications.
Arjan A van de Loosdrecht. Department of Hematology, VU Institute of Cancer and Immunolgy (V-ICI), VU University Medical Centre, Amsterdam, Netherlands
Flow cytometry in myelodysplastic syndromes: The WHO classification 2008 contributes to a more refined classification and prognostication of myelodysplastic syndromes (MDS). Since flow cytometry (FC) can identify aberrancies in granulocytic and monocytic lineages that are not recognised by cytology (WHO), FC might be instrumental in improving the classification of MDS. FC is even considered as co-criterion when regular diagnostic criteria are not met. Recently, Consensus was reached regarding cell sampling, handling and processing. Minimal combinations of antibodies that enable analysis of aberrant immunophenotypes and thus dysplasia are defined. Examples of aberrancies are altered numbers of CD34 precursors, altered expression of markers on myeloid blasts, maturing myeloid cells, monocytes or erythroid precursors and the expression of lineage infidelity markers.
In a recent retrospective study in patients with low and intermediate-1 risk MDS (RA, RARS, RCMD, RCMD-RS) FC identified aberrancies in granulopoiesis and monocytopoiesis in >90% of low/int-I risk MDS. In the majority of cases abnormal relations between CD13, CD16, CD11b, CD15, CD10 and HLA-DR are prominent in the granulopoiesis. In approximately one third of MDS cases striking monocytopenia is observed and in >60% abnormal surface expression of CD14, CD36 is found. Of note, dysplasia in monocytes is very difficult to recognise by cytology. In approximately 40% of MDS cases lineage infidelity antigen expression is detectable (co-expression of CD5, CD7, CD19, TdT or CD56 on CD34 myeloid blasts). The number of flow cytometric aberrancies can be translated into a MDS flow-score. A significant increase in the MDS flow-score among WHO subgroups from RA /-RS, RCMD /-RS towards RAEB-1/-2 is a common feature. Within IPSS subgroups flow-scores are highly heterogeneous which might indicate separate disease entities within each IPSS subgroup. Furthermore, the MDS flow-score identifies patients with a worse clinical outcome after allogeneic stem cell transplantation. Interestingly, a significant increase in the MDS dysplasia flow-score is observed between non-transfusion-dependent low/int-I risk patients and patients in progression to advanced MDS. In approximately 70% of the patients with transfusion-dependency and/or in progressive disease, lineage infidelity markers are detected on myeloid blasts, in contrast to non-transfusion dependent patients. Importantly, even in patients with uni-lineage dysplasia, e.g. RA /-RS and MDS-U, additional FC aberrancies are identified including lineage infidelity Ag expression on myeloid blasts in 30% of the cases. Within the pure-RA /-RS subgroup only patients with infidelity marker expression on myeloid blasts are transfusion dependent [3]. In a prospective study, selected parameters concerning percentages and/or aberrancies of myeloid blasts, progenitor B cells, and side scatter properties of granulocytes might discriminate MDS from non-clonal bone marrow diseases. Another parameter of importance in the distinction between normal and dysplastic bone marrow in MDS is the reduced expression of CD38 on CD34 bone marrow cells.
Since flow cytometric analysis of MDS bone marrow samples can identify clinically relevant subgroups regarding transfusion dependency and disease progression, we addressed the question whether flow cytometry was instrumental in predicting response to a standardized Epo/G-CSF regimen. In forty-six patients with low and intermediate-I risk MDS that were treated with Epo/G-CSF according to ELNet treatment guidelines, low Epo level and low transfusion need were associated with response to Epo/G-CSF. Interestingly, aberrant phenotype of myeloid blasts identified non-responders among patients with highest response probability according to the validated predictive model of Hellstr
Arjan A van de Loosdrecht. Department of Hematology, VU Institute of Cancer and Immunolgy (V-ICI), VU University Medical Centre, Amsterdam, Netherlands
Flow cytometry in myelodysplastic syndromes: The WHO classification 2008 contributes to a more refined classification and prognostication of myelodysplastic syndromes (MDS). Since flow cytometry (FC) can identify aberrancies in granulocytic and monocytic lineages that are not recognised by cytology (WHO), FC might be instrumental in improving the classification of MDS. FC is even considered as co-criterion when regular diagnostic criteria are not met. Recently, Consensus was reached regarding cell sampling, handling and processing. Minimal combinations of antibodies that enable analysis of aberrant immunophenotypes and thus dysplasia are defined. Examples of aberrancies are altered numbers of CD34 precursors, altered expression of markers on myeloid blasts, maturing myeloid cells, monocytes or erythroid precursors and the expression of lineage infidelity markers.
In a recent retrospective study in patients with low and intermediate-1 risk MDS (RA, RARS, RCMD, RCMD-RS) FC identified aberrancies in granulopoiesis and monocytopoiesis in >90% of low/int-I risk MDS. In the majority of cases abnormal relations between CD13, CD16, CD11b, CD15, CD10 and HLA-DR are prominent in the granulopoiesis. In approximately one third of MDS cases striking monocytopenia is observed and in >60% abnormal surface expression of CD14, CD36 is found. Of note, dysplasia in monocytes is very difficult to recognise by cytology. In approximately 40% of MDS cases lineage infidelity antigen expression is detectable (co-expression of CD5, CD7, CD19, TdT or CD56 on CD34 myeloid blasts). The number of flow cytometric aberrancies can be translated into a MDS flow-score. A significant increase in the MDS flow-score among WHO subgroups from RA /-RS, RCMD /-RS towards RAEB-1/-2 is a common feature. Within IPSS subgroups flow-scores are highly heterogeneous which might indicate separate disease entities within each IPSS subgroup. Furthermore, the MDS flow-score identifies patients with a worse clinical outcome after allogeneic stem cell transplantation. Interestingly, a significant increase in the MDS dysplasia flow-score is observed between non-transfusion-dependent low/int-I risk patients and patients in progression to advanced MDS. In approximately 70% of the patients with transfusion-dependency and/or in progressive disease, lineage infidelity markers are detected on myeloid blasts, in contrast to non-transfusion dependent patients. Importantly, even in patients with uni-lineage dysplasia, e.g. RA /-RS and MDS-U, additional FC aberrancies are identified including lineage infidelity Ag expression on myeloid blasts in 30% of the cases. Within the pure-RA /-RS subgroup only patients with infidelity marker expression on myeloid blasts are transfusion dependent [3]. In a prospective study, selected parameters concerning percentages and/or aberrancies of myeloid blasts, progenitor B cells, and side scatter properties of granulocytes might discriminate MDS from non-clonal bone marrow diseases. Another parameter of importance in the distinction between normal and dysplastic bone marrow in MDS is the reduced expression of CD38 on CD34 bone marrow cells.
Since flow cytometric analysis of MDS bone marrow samples can identify clinically relevant subgroups regarding transfusion dependency and disease progression, we addressed the question whether flow cytometry was instrumental in predicting response to a standardized Epo/G-CSF regimen. In forty-six patients with low and intermediate-I risk MDS that were treated with Epo/G-CSF according to ELNet treatment guidelines, low Epo level and low transfusion need were associated with response to Epo/G-CSF. Interestingly, aberrant phenotype of myeloid blasts identified non-responders among patients with highest response probability according to the validated predictive model of Hellstr
Flow cytometry in myelodysplastic syndromes. Definitions, Clinical and Diagnostic Applications.
Arjan A van de Loosdrecht. Department of Hematology, VU Institute of Cancer and Immunolgy (V-ICI), VU University Medical Centre, Amsterdam, Netherlands
Flow cytometry in myelodysplastic syndromes: The WHO classification 2008 contributes to a more refined classification and prognostication of myelodysplastic syndromes (MDS). Since flow cytometry (FC) can identify aberrancies in granulocytic and monocytic lineages that are not recognised by cytology (WHO), FC might be instrumental in improving the classification of MDS. FC is even considered as co-criterion when regular diagnostic criteria are not met. Recently, Consensus was reached regarding cell sampling, handling and processing. Minimal combinations of antibodies that enable analysis of aberrant immunophenotypes and thus dysplasia are defined. Examples of aberrancies are altered numbers of CD34 precursors, altered expression of markers on myeloid blasts, maturing myeloid cells, monocytes or erythroid precursors and the expression of lineage infidelity markers.
In a recent retrospective study in patients with low and intermediate-1 risk MDS (RA, RARS, RCMD, RCMD-RS) FC identified aberrancies in granulopoiesis and monocytopoiesis in >90% of low/int-I risk MDS. In the majority of cases abnormal relations between CD13, CD16, CD11b, CD15, CD10 and HLA-DR are prominent in the granulopoiesis. In approximately one third of MDS cases striking monocytopenia is observed and in >60% abnormal surface expression of CD14, CD36 is found. Of note, dysplasia in monocytes is very difficult to recognise by cytology. In approximately 40% of MDS cases lineage infidelity antigen expression is detectable (co-expression of CD5, CD7, CD19, TdT or CD56 on CD34 myeloid blasts). The number of flow cytometric aberrancies can be translated into a MDS flow-score. A significant increase in the MDS flow-score among WHO subgroups from RA /-RS, RCMD /-RS towards RAEB-1/-2 is a common feature. Within IPSS subgroups flow-scores are highly heterogeneous which might indicate separate disease entities within each IPSS subgroup. Furthermore, the MDS flow-score identifies patients with a worse clinical outcome after allogeneic stem cell transplantation. Interestingly, a significant increase in the MDS dysplasia flow-score is observed between non-transfusion-dependent low/int-I risk patients and patients in progression to advanced MDS. In approximately 70% of the patients with transfusion-dependency and/or in progressive disease, lineage infidelity markers are detected on myeloid blasts, in contrast to non-transfusion dependent patients. Importantly, even in patients with uni-lineage dysplasia, e.g. RA /-RS and MDS-U, additional FC aberrancies are identified including lineage infidelity Ag expression on myeloid blasts in 30% of the cases. Within the pure-RA /-RS subgroup only patients with infidelity marker expression on myeloid blasts are transfusion dependent [3]. In a prospective study, selected parameters concerning percentages and/or aberrancies of myeloid blasts, progenitor B cells, and side scatter properties of granulocytes might discriminate MDS from non-clonal bone marrow diseases. Another parameter of importance in the distinction between normal and dysplastic bone marrow in MDS is the reduced expression of CD38 on CD34 bone marrow cells.
Since flow cytometric analysis of MDS bone marrow samples can identify clinically relevant subgroups regarding transfusion dependency and disease progression, we addressed the question whether flow cytometry was instrumental in predicting response to a standardized Epo/G-CSF regimen. In forty-six patients with low and intermediate-I risk MDS that were treated with Epo/G-CSF according to ELNet treatment guidelines, low Epo level and low transfusion need were associated with response to Epo/G-CSF. Interestingly, aberrant phenotype of myeloid blasts identified non-responders among patients with highest response probability according to the validated predictive model of Hellstr
Arjan A van de Loosdrecht. Department of Hematology, VU Institute of Cancer and Immunolgy (V-ICI), VU University Medical Centre, Amsterdam, Netherlands
Flow cytometry in myelodysplastic syndromes: The WHO classification 2008 contributes to a more refined classification and prognostication of myelodysplastic syndromes (MDS). Since flow cytometry (FC) can identify aberrancies in granulocytic and monocytic lineages that are not recognised by cytology (WHO), FC might be instrumental in improving the classification of MDS. FC is even considered as co-criterion when regular diagnostic criteria are not met. Recently, Consensus was reached regarding cell sampling, handling and processing. Minimal combinations of antibodies that enable analysis of aberrant immunophenotypes and thus dysplasia are defined. Examples of aberrancies are altered numbers of CD34 precursors, altered expression of markers on myeloid blasts, maturing myeloid cells, monocytes or erythroid precursors and the expression of lineage infidelity markers.
In a recent retrospective study in patients with low and intermediate-1 risk MDS (RA, RARS, RCMD, RCMD-RS) FC identified aberrancies in granulopoiesis and monocytopoiesis in >90% of low/int-I risk MDS. In the majority of cases abnormal relations between CD13, CD16, CD11b, CD15, CD10 and HLA-DR are prominent in the granulopoiesis. In approximately one third of MDS cases striking monocytopenia is observed and in >60% abnormal surface expression of CD14, CD36 is found. Of note, dysplasia in monocytes is very difficult to recognise by cytology. In approximately 40% of MDS cases lineage infidelity antigen expression is detectable (co-expression of CD5, CD7, CD19, TdT or CD56 on CD34 myeloid blasts). The number of flow cytometric aberrancies can be translated into a MDS flow-score. A significant increase in the MDS flow-score among WHO subgroups from RA /-RS, RCMD /-RS towards RAEB-1/-2 is a common feature. Within IPSS subgroups flow-scores are highly heterogeneous which might indicate separate disease entities within each IPSS subgroup. Furthermore, the MDS flow-score identifies patients with a worse clinical outcome after allogeneic stem cell transplantation. Interestingly, a significant increase in the MDS dysplasia flow-score is observed between non-transfusion-dependent low/int-I risk patients and patients in progression to advanced MDS. In approximately 70% of the patients with transfusion-dependency and/or in progressive disease, lineage infidelity markers are detected on myeloid blasts, in contrast to non-transfusion dependent patients. Importantly, even in patients with uni-lineage dysplasia, e.g. RA /-RS and MDS-U, additional FC aberrancies are identified including lineage infidelity Ag expression on myeloid blasts in 30% of the cases. Within the pure-RA /-RS subgroup only patients with infidelity marker expression on myeloid blasts are transfusion dependent [3]. In a prospective study, selected parameters concerning percentages and/or aberrancies of myeloid blasts, progenitor B cells, and side scatter properties of granulocytes might discriminate MDS from non-clonal bone marrow diseases. Another parameter of importance in the distinction between normal and dysplastic bone marrow in MDS is the reduced expression of CD38 on CD34 bone marrow cells.
Since flow cytometric analysis of MDS bone marrow samples can identify clinically relevant subgroups regarding transfusion dependency and disease progression, we addressed the question whether flow cytometry was instrumental in predicting response to a standardized Epo/G-CSF regimen. In forty-six patients with low and intermediate-I risk MDS that were treated with Epo/G-CSF according to ELNet treatment guidelines, low Epo level and low transfusion need were associated with response to Epo/G-CSF. Interestingly, aberrant phenotype of myeloid blasts identified non-responders among patients with highest response probability according to the validated predictive model of Hellstr
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