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Ferrata Storti Foundation
Haematologica 2019 Volume 104(12):2382-2390
Myelodysplastic Syndromes
Flow cytometric analysis of neutrophil myeloperoxidase expression in peripheral blood for ruling out myelodysplastic syndromes: a diagnostic accuracy study
Tatiana Raskovalova,1 Marc G. Berger,2,3 Marie-Christine Jacob,1 Sophie Park,4,5 Lydia Campos,6 Carmen Mariana Aanei,6 Julie Kasprzak,2 Bruno Pereira,7 José Labarère,8,9 Jean-Yves Cesbron1,9 and Richard Veyrat-Masson2
1
Laboratoire d’Immunologie, Grenoble University Hospital, Université Grenoble Alpes,
2
F-38043 Grenoble; Service d’Hématologie Biologique, Hopital Estaing, Centre
Hospitalier Universitaire de Clermont-Ferrand, F-63003 Clermont-Ferrand; 3Université Clermont Auvergne, EA 7453 CHELTER, F-63000 Clermont-Ferrand; 4Clinique Universitaire d'Hématologie, Grenoble University Hospital, F-38043 Grenoble; 5Institute for Advanced Biosciences (IAB), INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble; 6Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Saint-Etienne, F- 42055, Saint-Etienne; 7Biostatistics Unit, Direction de la Recherche Clinique (DRCI), Centre Hospitalier Universitaire de Clermont-Ferrand, F-63003 Clermont-Ferrand; 8 Quality of Care Unit, INSERM CIC 1406, Grenoble University Hospital, F-38043 Grenoble and 9TIMC-IMAG, CNRS UMR 5525, Université Grenoble Alpes, F-38043 Grenoble, France
ABSTRACT
Suspicion of myelodysplastic syndromes (MDS) is one of the com- monest reasons for bone marrow aspirate in elderly patients present- ing with persistent peripheral blood (PB) cytopenia of unclear etiolo- gy. A PB assay that accurately rules out MDS would have major benefits. The diagnostic accuracy of the intra-individual robust coefficient of vari- ation (RCV) for neutrophil myeloperoxidase (MPO) expression measured by flow cytometric analysis in PB was evaluated in a retrospective deriva- tion study (44 MDS cases and 44 controls) and a prospective validation study (68 consecutive patients with suspected MDS). Compared with controls, MDS cases had higher median RCV values for neutrophil MPO expression (40.2% vs. 30.9%; P<0.001). The area under the receiver oper- ating characteristic curve estimates were 0.94 [95% confidence interval (CI): 0.86-0.97] and 0.87 (95%CI: 0.76-0.94) in the derivation and valida- tion studies, respectively. A RCV lower than 30% ruled out MDS with 100% sensitivity (95%CI: 78-100%) and 100% negative predictive value (95%CI: 83-100%) in the prospective validation study. Neutrophil MPO expression measured by flow cytometric analysis in PB might obviate the need for invasive bone marrow aspirate and biopsy for up to 29% of patients with suspected MDS.
Introduction
Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal bone marrow (BM) neoplasms that predominate in the elderly.1,2 The diagnosis of MDS is based on peripheral blood (PB) cytopenia and morphological dysplasia for one or more hematopoietic cell lineages.1,3,4 Cytopenia is evidenced with hemogram while dysplasia requires BM aspirate, which is an invasive procedure.1,2,5
Because of the limited prevalence of disease among subjects referred for suspect- ed MDS,6 many patients are exposed to unnecessary BM aspiration with the asso- ciated discomfort and risk. Therefore, an objective assay based on a PB sample that accurately discriminates MDS from other cytopenia etiologies is highly desirable. In this context, a few studies have investigated the value of flow cytometric analy- sis for detecting aberrant phenotypic expression of PB leukocytes in the diagnostic work-up of MDS.7-9 Although promising, these studies lacked replication of their
Correspondence:
TATIANA RASKOVALOVA
TRaskovalova@chu-grenoble.fr
Received: July 18, 2018. Accepted: April 18, 2019. Pre-published: April 19, 2019.
doi:10.3324/haematol.2018.202275
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/12/2382
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