Flow Cytometric Analysis of Peripheral Blood Neutrophil Myeloperoxidase Expression for Ruling Out Myelodysplastic Syndromes: Protocol for a Diagnostic Accuracy Study

NCT05175469 | Recruiting

• 2 other identifiers: 38RC21.1452021-A01101-40
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 8

Brief Summary

Myelodysplastic syndromes (MDS) are clonal bone marrow neoplasms characterized by dysplasia and ineffective hematopoiesis leading to peripheral blood cytopenias, with an increased risk of progression to acute myeloid leukemia. The conventional diagnostic work-up of MDS relies on cytomorphological evaluation of bone marrow, which may be complemented by conventional cytogenetic, flow cytometry, and molecular analysis by next generation sequencing techniques. Suspicion of MDS is the commonest reason for bone marrow aspirate in older patients with unexplained peripheral blood cytopenias. Yet many patients are exposed to unnecessary bone marrow aspiration-related discomfort and harms, because of the limited prevalence of disease among subjects referred for suspected MDS. In this context, a valid and reliable assay based on peripheral blood sample that accurately discriminates MDS from other cytopenia etiologies without requiring invasive bone marrow aspiration is warranted. The accuracy of peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis for the diagnosis of MDS is supported by three primary studies totaling 211 individuals. An intra-individual robust coefficient of variation (RCV) value for neutrophil myeloperoxidase expression lower than 30.0% accurately ruled out MDS, with both sensitivity and negative predictive value point estimates of 100%, in consecutive patients with suspected disease. This biomarker might obviate the need for cytomorphological evaluation of bone marrow aspirate for up to 35% of patients referred for suspected MDS. Although promising, these preliminary results require replication in an independent external validation sample. The broad aim of the multicenter MPO-MDS-Valid study project is to prospectively validate the diagnostic accuracy of intra-individual RCV for peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis among consecutive patients referred for suspected MDS.

Conditions

Myelodysplastic Syndromes

Keywords

Myelodysplastic syndromes; Diagnostic accuracy study; Flow cytometry analysis; Myeloperoxidase; Peripheral blood sample; Additional relevant MeSH terms: Preleukemia, Syndrome, Disease, Pathologic Processes

Outcome Measures

Primary Outcomes (1)

• Area under the receiver operating characteristic (ROC) curve

  The area under the ROC curve point estimate along with 95% confidence interval will quantify the accuracy of the index test (i.e., intra-individual RCV for neutrophil myeloperoxidase expression in peripheral blood) for the diagnosis of myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). The reference diagnosis will be established by cytomorphological evaluation of bone marrow aspirate performed by independent experienced hematopathologists blinded to the index test results. Morphologic assessment may be complemented by bone marrow flow cytometric score, karyotype, and molecular profiling, where relevant.

  Baseline

Secondary Outcomes (2)

• Negative predictive value

  Baseline

• Prevalence of alternate diagnoses for true negative cases

  Baseline

Interventions

Flow cytometric analysis of neutrophil myeloperoxidase expression DIAGNOSTIC_TEST

Performance of flow cytometric analysis of neutrophil myeloperoxidase expression in peripheral blood samples will be blinded to the reference standard. Peripheral blood samples will be collected in 5 ml (EDTA) anticoagulant plastic tubes and processed on the same day of collection. Blood samples will be incubated with a panel of antibodies conjugated to fluorochromes, according to the manufacturers' recommendations. At least 10,000 cell events will be acquired on a 3-laser, 8/12-color flow cytometer and analyzed using flow cytometry software. Myeloperoxidase expression in the peripheral blood neutrophil population within an individual subject will be expressed as intra-individual robust coefficient of variation (RCV).

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult, Older Adult

You may qualify if:

• Age at enrollment ≥18 years
• Referral for suspicion of myelodysplastic syndrome
• Indication for bone marrow examination
• ≥1 peripheral blood cytopenia defined by hemoglobin concentration \<12 g/dL for female and \<13g/dL for male patients, platelet count \<150 x109/L, absolute neutrophil count \<1.8 x109/L
• Inpatient or outpatient care

You may not qualify if:

• Refusal to participate
• History of or active documented MDS or CMML
• Enrollment in intensive or critical care unit
• Incarcerated or individuals protected by French regulation (Article L1121.5 and following, Code de la Santé Publique)
• Not affiliated with social security system
• Previous enrollment in the study

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (8)

University Hospital, Clermont-Ferrand

Clermont-Ferrand, 63003, France

NOT YET RECRUITING

Grenoble_Alpes UniversityHospital

Grenoble, 38043, France

RECRUITING

University Hospital Lyon Sud, HCL

Lyon, 69310, France

RECRUITING

Institut Paoli Calmettes

Marseille, 13009, France

RECRUITING

University Hospital Saint-Eloi

Montpellier, 34090, France

RECRUITING

Chu Nantes

Nantes, 44093, France

RECRUITING

University Hospital NICE

Nice, 06202, France

RECRUITING

University Hospital, Saint-Étienne

Saint-Etienne, 42055, France

RECRUITING

Related Publications (1)

• Planta C, Bret C, Manzoni D, Lhoumeau AC, Mayeur Rousse C, Ticchioni M, Campos L, Eischen A, Gonnet N, Merle R, Seigneurin A, Paul F, Comte E, Allieri-Rosenthal A, Tondeur S, Regnart C, Jacob MC, Labarere J, Park S, Raskovalova T. Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in myelodysplastic neoplasms (MPO-MDS-Valid): protocol for a multicentre diagnostic accuracy study. BMJ Open. 2024 Jun 17;14(6):e081200. doi: 10.1136/bmjopen-2023-081200.

  PMID: 38889946 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Syndrome; Disease; Pathologic Processes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Pathological Conditions, Signs and Symptoms

Study Officials

• Tatiana RASKOVALOVA

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tatiana RASKOVALOVA

CONTACT

04 76 76 63 34; traskovalova@chu-grenoble.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2021
• First Posted: January 3, 2022
• Study Start: March 1, 2022
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 24 months after publication of the main findings of the final dataset. No end date.
• Access Criteria: De-identified data will be available for individual participant data meta-analysis purpose. Researchers should submit a methodologically sound proposal that complies with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement. Proposals should be directed to TRaskovalova@chu-grenoble.fr. Data requestors will need to sign a data access agreement.

Locations

FR (8)