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Faculty of Medical Sciences

The diagnostic value of flow cytometry for bone marrow aspirates in making the diagnosis myelodysplastic syndrome

Jong, M.R. de (Mark Roland) (2013) The diagnostic value of flow cytometry for bone marrow aspirates in making the diagnosis myelodysplastic syndrome. thesis, Medicine.

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Abstract

Introduction: The myelodysplastic syndrome (MDS) is a monoclonal stem cell disease which may cause peripheral cytopenias such as anaemia, thrombocytopenia and neutropenia. MDS is accompanied by an increased risk to develop acute myeloid leukaemia (AML). The diagnosis is based on scoring dysplasia with morphology. This method is subjective and subject to inter observer variability. To find a more objective way to score dysplasia flow cytometry is evaluated for its diagnostic value. Material and methods: All patients with a cytopenia in whom a bone marrow aspirate was undertaken, were evaluated with a first colouring to see which diagnosis was most likely. If MDS was part of the differential diagnosis, the patient was included. We then used flow cytometry to search for aberrancies matching MDS. Four cardinal parameters were used to screen for MDS: the percentage of precursor B cells of all CD34 positive cells, the side scatter ratio between granulocytes and lymphocytes, the CD45 ratio between myeloblasts and lymphocytes and the percentage of myeloblasts. To increase the sensitivity and specificity three additional parameters were added: the expression of CD11b, CD56 and CD15 on myeloblasts. Based on these parameters the total sensitivity and specificity, likelihood ratio with positive and negative predictive value were calculated. Subgroups within the MDS group (n=78) and the pathological controls (n=128) were compared to see whether there was a pattern in marker expression. Based on the total flow score we sought to see whether a high flow score correlates with a higher chance of finding MDS. Retrospectively we investigated the value of expression of CD7 on myeloblasts as a diagnostic parameters on the advice of the Dutch MDS group. Results: Just the cardinal parameters provide a low sensitivity and specificity. Adding the other four parameters increased the sensitivity and specificity to 74% and 71% respectively. Flow cytometry demonstrated a clear distinction between low grade and high grade MDS. It showed little difference between low grade MDS and normal bone marrows and no significantly different markers were found between high grade MDS and acute myeloid leukaemia (AML). However, a high total flow score did not mean an significant higher chance of finding MDS. CD7 did not significantly differ between any of the subgroups and even resulted in a worse sensitivity and specificity for finding MDS. Conclusion: Flow cytometry is an objective tool to make a diagnosis of MDS with a reasonable sensitivity and specificity within a population offered to a large non-academic hospital. The value of flowcytometry is more outspoken when another diagnosis than MDS is yet suspected morphologically. However the total flow score is an unreliable diagnostic tool. The expression of CD7 has no further added value. Flow cytometry shows the heterogeneity of MDS as a clinical entity and should therefore be investigated for its value in risk management.

Item Type: Thesis (Thesis)
Supervisor name: Facultair begeleider: and Nijholt. dr. I.M.
Supervisor name: Plaatselijk begeleiders: and Kuiper-Kramer dr. P.A. and en and Moshaver, dr. B. and Locatie: and Klinisch-Chemisch Laboratorium Isala klinieken Zwolle
Faculty: Medical Sciences
Date Deposited: 25 Jun 2020 10:44
Last Modified: 25 Jun 2020 10:44
URI: https://umcg.studenttheses.ub.rug.nl/id/eprint/603

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