In a recent article published in the journal BMJ Open, a research team from Grenoble, France, described the protocol for an ongoing study on a potential diagnostic approach for myelodysplastic syndromes (MDS).
Evaluation for MDS is currently a common reason for undergoing bone marrow aspiration in patients who are elderly and who show persistent blood cytopenia without a clear cause identified. “However, many patients are exposed to unnecessary bone marrow aspiration-related discomfort and harm because of the relatively low prevalence of disease among subjects who are referred for suspected MDS,” the study investigators explained in their report.
In their report, the researchers explained that flow cytometry-based analysis of peripheral blood neutrophil myeloperoxidase expression may circumvent the need for bone marrow aspiration in identifying MDS. To explore this question, they established the MPO-MDS-Develop study (ClinicalTrials.gov Identifier: NCT04399018), conducted at Grenoble University Hospital in Grenoble, France, and involving participants who are unselected, consecutive adults being evaluated based on suspicion of MDS.
In this study, the researchers are evaluating a hypothesis that a flow cytometry-based method involving a single-use tube containing lyophilized reagents will provide the accuracy needed to reject a diagnosis of MDS by analysis of peripheral blood neutrophil myeloperoxidase expression, in addition to other hypotheses. The study will examine an approach involving a product called Lyotube Stain 468 (BD Biosciences, San Jose, California, USA), compared with an approach using a laboratory-developed liquid reagent-based test, in evaluating possible MDS. A goal is to determine the level of agreement and comparative accuracy with these approaches.
The Lyotube Stain 468 product includes dried reagents associated with 5 fluorochromes, while the laboratory-developed test uses liquid reagents associated with the same fluorochromes. With both approaches, an antimyeloperoxidase antibody is applied to samples, and myeloperoxidase expression from peripheral blood neutrophils is measured. The primary study outcome is a reference diagnosis of MDS determined through bone marrow examination independently performed by 2 hematopathologists who are blinded to the findings of the other diagnostic approaches being evaluated in the study.
The planned population size for the study is 103 participants. A formal interim analysis is not planned, and P-values below 0.05 will be considered significant in statistical analyses. A prespecified threshold of 30.0% for a measure called the intraindividual robust coefficient of variation will be applied to evaluations of diagnostic accuracy.
The researchers identified the strengths of this study to include the use of an adequate reference approach to MDS diagnosis, limited spectrum bias owing to enrollment of unselected consecutive patients, and a prespecified threshold for evaluation of diagnostic accuracy. Limitations of the study that they identified include the single-center nature of the study setting, in addition to conventional cytogenetic and molecular profiling approaches not being available to all patients in the study.
Participants in this study were enrolled between July 27, 2020, and September 30, 2021. The study completion date is expected to be December 31, 2023.
Raskovalova T, Scheffen L, Jacob MC, et al. Flow cytometry lyophilised-reagent tube for quantifying peripheral blood neutrophil myeloperoxidase expression in myelodysplastic syndromes (MPO-MDS-Develop): protocol for a diagnostic accuracy study. BMJ Open. 2022;12(10):e065850. doi:10.1136/bmjopen-2022-065850