Flow Cytometric Analysis of Peripheral Blood Neutrophil Myeloperoxidase Expression and Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal bone marrow neoplasms that predominate in the elderly, with a median age at diagnosis of 70 years. MDS are characterized by peripheral blood cytopenia and morphologic dysplasia for one or more hematopoietic cell lineage, reflecting ineffective hematopoiesis. The diagnostic work-up of MDS includes a bone marrow aspirate and biopsy, which is an invasive procedure, for cytomorphologic and cytogenetic evaluations. Because the prevalence of disease is lower than 20% in subjects referred for suspected MDS, many patients are exposed to unnecessary bone marrow aspiration-related discomfort and harms. An objective assay is highly desirable for accurately ruling out MDS based on peripheral blood samples, which may obviate the need for invasive bone marrow aspiration and biopsy in patients with negative results. Few studies have investigated the value of peripheral blood flow cytometric analysis for the diagnosis of MDS and/or chronic myelomonocytic leukemia (CMML). Although promising, these studies lacked replication of their results, used a case-control design, which was prone to spectrum bias, or yielded imprecise diagnostic accuracy estimates due to relatively limited sample sizes. Anecdotal evidence supports the potential of flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression for the diagnosis of MDS and CMML. Myeloperoxidase is an enzyme synthetized during myeloid differentiation that constitutes the major component of neutrophil azurophilic granules. Myeloperoxidase expression may reflect neutrophil hypogranulation, which is a classical although subjective dysplastic feature of MDS. Flow cytometric analysis of myeloperoxidase expression in bone marrow neutrophil granulocytes has been used for discriminating low versus high grade MDS. Yet a study reporting on the accuracy of flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression for the diagnosis of MDS is still lacking, to our knowledge. In this study, the investigators hypothesize that flow cytometric analysis of neutrophil myeloperoxidase expression in peripheral blood may accurately rule out MDS and obviate the need for bone marrow aspiration and biopsy, with sensitivity approaching 100%, in routine practice. In this observational diagnostic accuracy study, burden will be null for recruited patients. No specific intervention is assigned to participants. All diagnostic testing, procedures, and medication ordering are performed at the discretion of attending physicians. Flow cytometry analysis of peripheral blood neutrophil myeloperoxidase expression will not require additional blood sample. A test result will have no impact on patient management. No follow-up visits are planned in this cross-sectional study.

Sex

All

Minimum age

50 Years

Inclusion Criteria:

* Age ≥50 years;
* Clinical suspicion of myelodysplastic syndromes (MDS) and / or chronic myelomonocytic leukemia (CMML);
* Peripheral blood cytopenia defined by hemoglobin concentration \<10 g/dL, platelet count \<100 x109/L, and/or absolute neutrophil count \<1.8 x109/L.

Exclusion Criteria:

* History of or active documented MDS or CMML;
* Admission to the intensive care unit;
* Suspicion of hematological disease other than MDS requiring bone marrow aspirate and/or biopsy (i.e., acute leukemia,…);
* Absolute neutrophil count \<0.5 x109/L;
* Not affiliated with a social security system;
* Homelessness;
* Incarcerated;
* Inability to understand research information and/or to provide non-opposition, because of language restriction, dementia, or altered mental status;
* Refusal to participate;
* Previous enrollment in the study.

• DERIVEDRaskovalova T, Scheffen L, Jacob MC, Vettier C, Bulabois B, Szymanski G, Chevalier S, Gonnet N, Park S, Labarere J. Comparative diagnostic accuracy between simplified and original flow cytometric gating strategies for peripheral blood neutrophil myeloperoxidase expression in ruling out myelodysplastic syndromes. PLoS One. 2022 Nov 18;17(11):e0276095. doi: 10.1371/journal.pone.0276095. eCollection 2022. PMID 36399441
• DERIVEDRaskovalova T, Jacob MC, Bulabois CE, Mariette C, Scheffen L, Park S, Labarere J. Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression for ruling out myelodysplastic syndromes: a prospective validation study. Ann Hematol. 2021 May;100(5):1149-1158. doi: 10.1007/s00277-021-04446-7. Epub 2021 Feb 10. PMID 33569703