Correspondence Myelodysplastic Syndromes To the Editor: In a comprehensive review ar- The author replies: Raskovalova et al. question ticle, Cazzola (Oct. 1 issue)1 describes the con- the routine use of bone marrow examination in ventional approach to the diagnosis of myelo- older patients with unexplained peripheral-blood dysplastic syndromes (MDS) that relies on cytopenia who are referred for suspected MDS. morphologic assessment of bone marrow and Raskovalova and colleagues developed a screen- cytogenetics. Suspicion of MDS is the most com- ing test based on flow cytometric evaluation of mon reason for bone marrow aspiration and bi- neutrophil myeloperoxidase in peripheral blood.1 opsy in older patients. However, because of the With the use of this test, MDS was ruled out in low prevalence of MDS among patients referred approximately 30% of patients without invasive for suspected MDS, many patients are unneces- examinations. Although the detection of dysplas- sarily exposed to the discomfort and potential tic cells by flow cytometry is an interesting ob- harms of these invasive procedures.2,3 Therefore, servation, independent validation of this approach an objective assay of a peripheral-blood sample is warranted before it can be reliably used for that accurately discriminates MDS from other clinical decision making. causes of unexplained cytopenia is warranted.4 Blood cytopenia is detected not only in MDS, We previously reported on the diagnostic ac- but also in several myeloid cancers and a few curacy of flow cytometric analysis of peripheral- lymphoid neoplasms.2 Bone marrow aspiration blood neutrophil myeloperoxidase expression in is minimally invasive and highly informative in ruling out MDS with 100% sensitivity (95% the diagnosis of myeloid cancers,3 and it should confidence interval [CI], 78 to 100) and a 100% therefore be considered in all patients with negative predictive value (95% CI, 83 to 100).5 unexplained peripheral-blood cytopenia. Bone This approach might obviate the need for mor- marrow biopsy is more invasive than bone phologic assessment of bone marrow in 29% of marrow aspiration, and it may be used in a patients (95% CI, 19 to 42) who are referred for more selective manner, especially in older pa- suspected MDS.5 These findings have been repli- tients. Finally, if a screening test of peripheral- cated in an external prospective validation sample.5 blood samples were to be developed, the best Tatiana Raskovalova, M.D. candidate would definitely be molecular profil- Marie-Christine Jacob, M.D. ing with a gene panel assay to detect somatic Sophie Park, M.D. mutations.4 University Grenoble Alpes Mario Cazzola, M.D. Grenoble, France traskovalova@ chu-grenoble . fr Fondazione IRCCS Policlinico San Matteo Drs. Raskovalova, Jacob, and Park report receiving research Pavia, Italy support (antibodies free of charge) from Becton Dickinson Bio- mario . cazzola@ unipv . it sciences. No other potential conflict of interest relevant to this Since publication of his article, the author reports no further letter was reported. potential conflict of interest. 1. Cazzola M. Myelodysplastic syndromes. N Engl J Med 2020; 1. Raskovalova T, Berger MG, Jacob M-C, et al. Flow cytometric 383: 1358-74. analysis of neutrophil myeloperoxidase expression in peripheral 2. Bain BJ. Morbidity associated with bone marrow aspiration blood for ruling out myelodysplastic syndromes: a diagnostic and trephine biopsy — a review of UK data for 2004. Haemato- accuracy study. Haematologica 2019; 104: 2382-90. logica 2006; 91: 1293-4. 2. Swerdlow SH, Campo E, Harris NL, et al., eds. WHO clas- 3. Brunetti GA, Tendas A, Meloni E, et al. Pain and anxiety as- sification of tumors of haematopoietic and lymphoid tissues. sociated with bone marrow aspiration and biopsy: a prospective Lyon, France: International Agency for Research on Cancer, study on 152 Italian patients with hematological malignancies. 2017. Ann Hematol 2011; 90: 1233-5. 3. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to 4. Boutault R, Peterlin P, Boubaya M, et al. A novel complete the World Health Organization classification of myeloid neo- blood count-based score to screen for myelodysplastic syndrome plasms and acute leukemia. Blood 2016; 127: 2391-405. in cytopenic patients. Br J Haematol 2018; 183: 736-46. 4. Malcovati L, Gallì A, Travaglino E, et al. Clinical signifi- 5. Raskovalova T, Berger MG, Jacob M-C, et al. Flow cytometric cance of somatic mutation in unexplained blood cytopenia. analysis of neutrophil myeloperoxidase expression in peripheral Blood 2017; 129: 3371-8. blood for ruling out myelodysplastic syndromes: a diagnostic accuracy study. Haematologica 2019; 104: 2382-90. DOI: 10.1056/NEJMc2032391 DOI: 10.1056/NEJMc2032391 Correspondence Copyright © 2020 Massachusetts Medical Society. 2590 n engl j med 383;26 nejm.org December 24, 2020 The New England Journal of Medicine Copyright © 2020 Massachusetts Medical Society. All rights reserved. .