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Published in: Annals of Hematology 5/2021

01-05-2021 | Myelodysplastic Syndrome | Original Article

Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression for ruling out myelodysplastic syndromes: a prospective validation study

Authors: Tatiana Raskovalova, Marie-Christine Jacob, Claude-Eric Bulabois, Clara Mariette, Laura Scheffen, Sophie Park, José Labarère

Published in: Annals of Hematology | Issue 5/2021

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Abstract

Suspicion of myelodysplastic syndromes (MDS) is the most common reason for bone marrow aspirate in elderly patients. This study aimed to prospectively validate the accuracy for flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in ruling out MDS. We enrolled 62 consecutive patients who were referred for suspected MDS, based on medical history and peripheral blood cytopenia. The accuracy of intra-individual robust coefficient of variation (RCV) for peripheral blood neutrophil myeloperoxidase expression was assessed with a prespecified 30% threshold. Cytomorphological evaluation of bone marrow aspirate performed by experienced hematopathologists confirmed MDS in 23 patients (prevalence, 37%), unconfirmed MDS in 32 patients (52%, including 3 patients with idiopathic cytopenia of undetermined significance (ICUS)), and was uninterpretable in 7 patients (11%). The median intra-individual RCV values for neutrophil myeloperoxidase expression in peripheral blood were 37.4% (range, 30.7–54.1), 29.2% (range, 28.1–32.1), and 29.1% (range, 24.7–37.8) for patients with confirmed suspicion of MDS, ICUS, and unconfirmed suspicion of MDS, respectively (P<0.001). The area under the ROC curve was 0.92 (95% confidence interval, 0.86–0.99). An intra-individual RCV value lower than 30% ruled out MDS for 35% (i.e., 19/55) patients referred for suspected disease, with 100% sensitivity (95% CI, 85–100%) and 100% negative predictive value (95% CI, 82–100%) estimates. This study shows that flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression might obviate the need for bone marrow aspirate for 35% of patients with suspected MDS. Trial registration: ClinicalTrials.​gov identifier: NCT03363399 (first posted on December 6, 2017)
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Literature
1.
2.
go back to reference Nachtkamp K, Stark R, Strupp C, Kündgen A, Giagounidis A, Aul C, Hildebrandt B, Haas R, Gattermann N, Germing U (2016) Causes of death in 2877 patients with myelodysplastic syndromes. Ann Hematol 95:937–944CrossRef Nachtkamp K, Stark R, Strupp C, Kündgen A, Giagounidis A, Aul C, Hildebrandt B, Haas R, Gattermann N, Germing U (2016) Causes of death in 2877 patients with myelodysplastic syndromes. Ann Hematol 95:937–944CrossRef
3.
go back to reference Zeidan AM, Shallis RM, Wang R, Davidoff A, Ma X (2019) Epidemiology of myelodysplastic syndromes: why characterizing the beast is a prerequisite to taming it. Blood Rev 34:1–15CrossRef Zeidan AM, Shallis RM, Wang R, Davidoff A, Ma X (2019) Epidemiology of myelodysplastic syndromes: why characterizing the beast is a prerequisite to taming it. Blood Rev 34:1–15CrossRef
4.
go back to reference Garcia-Manero G, Chien K, Montalban-Bravo G (2020) Myelodysplastic syndromes: 2021 update on diagnosis, risk-stratification and management. Am J Hematol 95:1399–1420CrossRef Garcia-Manero G, Chien K, Montalban-Bravo G (2020) Myelodysplastic syndromes: 2021 update on diagnosis, risk-stratification and management. Am J Hematol 95:1399–1420CrossRef
5.
go back to reference Fenaux P, Haase D, Santini V, Sanz GF, Platzbecker U, Mey U (2021) Myelodysplastic syndromes: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 32:142–156CrossRef Fenaux P, Haase D, Santini V, Sanz GF, Platzbecker U, Mey U (2021) Myelodysplastic syndromes: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 32:142–156CrossRef
6.
go back to reference Buckstein R, Jang K, Friedlich J, Zhang L, Reis M, Chesney A, Wells RA (2009) Estimating the prevalence of myelodysplastic syndromes in patients with unexplained cytopenias: a retrospective study of 322 bone marrows. Leuk Res 33:1313–1318CrossRef Buckstein R, Jang K, Friedlich J, Zhang L, Reis M, Chesney A, Wells RA (2009) Estimating the prevalence of myelodysplastic syndromes in patients with unexplained cytopenias: a retrospective study of 322 bone marrows. Leuk Res 33:1313–1318CrossRef
7.
go back to reference Gendron N, Zia Chahabi S, Poenou G, Rivet N, Belleville-Rolland T, Lemaire P et al (2019) Pain assessment and factors influencing pain during bone marrow aspiration: a prospective study. PLoS One 14:e0221534CrossRef Gendron N, Zia Chahabi S, Poenou G, Rivet N, Belleville-Rolland T, Lemaire P et al (2019) Pain assessment and factors influencing pain during bone marrow aspiration: a prospective study. PLoS One 14:e0221534CrossRef
8.
go back to reference Bain BJ (2006) Morbidity associated with bone marrow aspiration and trephine biopsy - a review of UK data for 2004. Haematologica 91:1293–1294PubMed Bain BJ (2006) Morbidity associated with bone marrow aspiration and trephine biopsy - a review of UK data for 2004. Haematologica 91:1293–1294PubMed
10.
go back to reference Boutault R, Peterlin P, Boubaya M, Sockel K, Chevallier P, Garnier A et al (2018) A novel complete blood count-based score to screen for myelodysplastic syndrome in cytopenic patients. Br J Haematol 183:736–746CrossRef Boutault R, Peterlin P, Boubaya M, Sockel K, Chevallier P, Garnier A et al (2018) A novel complete blood count-based score to screen for myelodysplastic syndrome in cytopenic patients. Br J Haematol 183:736–746CrossRef
11.
go back to reference Raskovalova T, Berger MG, Jacob MC, Park S, Campos L, Aanei CM et al (2019) Flow cytometric analysis of neutrophil myeloperoxidase expression in peripheral blood for ruling out myelodysplastic syndromes: a diagnostic accuracy study. Haematologica 104:2382–2390CrossRef Raskovalova T, Berger MG, Jacob MC, Park S, Campos L, Aanei CM et al (2019) Flow cytometric analysis of neutrophil myeloperoxidase expression in peripheral blood for ruling out myelodysplastic syndromes: a diagnostic accuracy study. Haematologica 104:2382–2390CrossRef
12.
go back to reference Sackett DL, Haynes RB (2002) The architecture of diagnostic research. BMJ 324:539–541CrossRef Sackett DL, Haynes RB (2002) The architecture of diagnostic research. BMJ 324:539–541CrossRef
13.
go back to reference Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L et al (2015) STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ 351:h5527CrossRef Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L et al (2015) STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ 351:h5527CrossRef
14.
go back to reference Della Porta MG, Picone C, Pascutto C, Malcovati L, Tamura H, Handa H et al (2012) Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study. Haematologica 97:1209–1217CrossRef Della Porta MG, Picone C, Pascutto C, Malcovati L, Tamura H, Handa H et al (2012) Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study. Haematologica 97:1209–1217CrossRef
15.
go back to reference Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127:2391–2405CrossRef Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127:2391–2405CrossRef
16.
go back to reference Valent P (2019) ICUS, IDUS, CHIP and CCUS: diagnostic criteria, separation from MDS and clinical implications. Pathobiology 86:30–38CrossRef Valent P (2019) ICUS, IDUS, CHIP and CCUS: diagnostic criteria, separation from MDS and clinical implications. Pathobiology 86:30–38CrossRef
17.
go back to reference Patnaik MM, Tefferi A (2020) Chronic myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management. Am J Hematol 95:97–115CrossRef Patnaik MM, Tefferi A (2020) Chronic myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management. Am J Hematol 95:97–115CrossRef
18.
go back to reference Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088CrossRef Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088CrossRef
19.
go back to reference Aires A, Teixeira MDA, Lau C, Moreira C, Spinola A, Mota A et al (2018) A pilot study on the usefulness of peripheral blood flow cytometry for the diagnosis of lower risk myelodysplastic syndromes: the “MDS thermometer”. BMC Hematol 18:6CrossRef Aires A, Teixeira MDA, Lau C, Moreira C, Spinola A, Mota A et al (2018) A pilot study on the usefulness of peripheral blood flow cytometry for the diagnosis of lower risk myelodysplastic syndromes: the “MDS thermometer”. BMC Hematol 18:6CrossRef
20.
go back to reference Cherian S, Moore J, Bantly A, Vergilio JA, Klein P, Luger S, Bagg A (2005) Peripheral blood MDS score: a new flow cytometric tool for the diagnosis of myelodysplastic syndromes. Cytometry B Clin Cytom 64:9–17CrossRef Cherian S, Moore J, Bantly A, Vergilio JA, Klein P, Luger S, Bagg A (2005) Peripheral blood MDS score: a new flow cytometric tool for the diagnosis of myelodysplastic syndromes. Cytometry B Clin Cytom 64:9–17CrossRef
21.
go back to reference Meyerson HJ, Osei E, Schweitzer K, Blidaru G, Edinger A, Balog A (2013) CD177 expression on neutrophils: in search of a clonal assay for myeloid neoplasia by flow cytometry. Am J Clin Pathol 140:658–669CrossRef Meyerson HJ, Osei E, Schweitzer K, Blidaru G, Edinger A, Balog A (2013) CD177 expression on neutrophils: in search of a clonal assay for myeloid neoplasia by flow cytometry. Am J Clin Pathol 140:658–669CrossRef
22.
go back to reference Rashidi HH, Xu X, Wang HY, Shafi NQ, Rameshkumar K, Messer K et al (2012) Utility of peripheral blood flow cytometry in differentiating low grade versus high grade myelodysplastic syndromes (MDS) and in the evaluation of cytopenias. Int J Clin Exp Pathol 5:224–230PubMedPubMedCentral Rashidi HH, Xu X, Wang HY, Shafi NQ, Rameshkumar K, Messer K et al (2012) Utility of peripheral blood flow cytometry in differentiating low grade versus high grade myelodysplastic syndromes (MDS) and in the evaluation of cytopenias. Int J Clin Exp Pathol 5:224–230PubMedPubMedCentral
23.
go back to reference Sandes AF, Yamamoto M, Matarraz S, Chauffaille Mde L, Quijano S, Lopez A et al (2012) Altered immunophenotypic features of peripheral blood platelets in myelodysplastic syndromes. Haematologica 97:895–902CrossRef Sandes AF, Yamamoto M, Matarraz S, Chauffaille Mde L, Quijano S, Lopez A et al (2012) Altered immunophenotypic features of peripheral blood platelets in myelodysplastic syndromes. Haematologica 97:895–902CrossRef
24.
go back to reference Selimoglu-Buet D, Wagner-Ballon O, Saada V, Bardet V, Itzykson R, Bencheikh L et al (2015) Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia. Blood 125:3618–3626CrossRef Selimoglu-Buet D, Wagner-Ballon O, Saada V, Bardet V, Itzykson R, Bencheikh L et al (2015) Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia. Blood 125:3618–3626CrossRef
25.
go back to reference Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155:529–536CrossRef Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155:529–536CrossRef
26.
go back to reference Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F et al (2016) Cytopenia levels for aiding establishment of the diagnosis of myelodysplastic syndromes. Blood 128:2096–2097CrossRef Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F et al (2016) Cytopenia levels for aiding establishment of the diagnosis of myelodysplastic syndromes. Blood 128:2096–2097CrossRef
Metadata
Title
Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression for ruling out myelodysplastic syndromes: a prospective validation study
Authors
Tatiana Raskovalova
Marie-Christine Jacob
Claude-Eric Bulabois
Clara Mariette
Laura Scheffen
Sophie Park
José Labarère
Publication date
01-05-2021
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 5/2021
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-021-04446-7

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