Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-14T16:55:36.988Z Has data issue: false hasContentIssue false

Chapter 8 - Myelodysplastic Syndromes

Published online by Cambridge University Press:  12 November 2020

Jon van der Walt ,
Attilio Orazi  and
Daniel A. Arber
By
Olga Weinberg  and
Robert Hasserjian
Jon van der Walt
Affiliation:
St Thomas’ Hospital, London
Attilio Orazi
Affiliation:
Texas Tech University
Daniel A. Arber
Affiliation:
University of Chicago
Get access

Summary

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of myeloid neoplasms defined by peripheral cytopaenia, morphologic dysplasia in one or more haematopoietic lineages, and genetic instability with risk of transformation to acute myeloid leukaemia (AML). A diagnosis of MDS requires the presence of cytopaenia, plus one or more of the following diagnostic features: morphologic evidence of dysplasia in >10% of cells involving at least one haematopoietic lineage, increased blasts, and/or an MDS-defining cytogenetic abnormality. Modern diagnosis of MDS was standardized by the French–American–British (FAB) cooperative group in 1982, which included the first standard descriptions of myelodysplasia [1], and was further refined in the World Health Organization (WHO) classification of 2001, which more specifically quantified dysplasia (Table 8.1) [2].

Keywords

Myelodysplasticcytopeniasideroblaststherapy-relatedimmunophenotypegeneticsprognosis
Type
Chapter
Information
Diagnostic Bone Marrow Haematopathology , pp. 107 - 126
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bennett, JM, Catovsky, D, Daniel, MT, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982 Jun;51(2):189–99.Google Scholar
Swerdlow, SH, Campo, E, Harris, NL, et al. (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press 2017, 106–20.Google Scholar
Greenberg, P, Cox, C, LeBeau, MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88.Google Scholar
Greenberg, PL, Tuechler, H, Schanz, J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood, 2012;120:2454–65.Google Scholar
Cogle, CR. Incidence and burden of the myelodysplastic syndromes. Curr Hematol Malig Rep. 2015;10(3):272–81.CrossRefGoogle ScholarPubMed
Bejar, R, Steensma, DP. Recent developments in myelodysplastic syndromes. Blood. 2014;124(18):2793–803.Google Scholar
Giralt, SA, Horowitz, M, Weisdorf, D, Cutler, C. Review of stem-cell transplantation for myelodysplastic syndromes in older patients in the context of the Decision Memo for Allogeneic Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndrome emanating from the Centers for Medicare and Medicaid Services. J Clin Oncol. 2011;29(5):566–72.Google Scholar
Strom, SS1, Gu, Y, Gruschkus, SK, Pierce, SA, Estey, EH. Risk factors of myelodysplastic syndromes: a case-control study. Leukemia. 2005;19(11):1912–18.Google Scholar
Ma, X, Lim, U, Park, Y, et al. Obesity, lifestyle factors, and risk of myelodysplastic syndromes in a large US cohort. Am J Epidemiol. 2009; 169(12):1492–9.Google Scholar
Nardi, V, Winkfield, KM, Ok, CY, et al. Acute myeloid leukemia and myelodysplastic syndromes after radiation therapy are similar to de novo disease and differ from other therapy-related myeloid neoplasms. J Clin Oncol. 2012; 30(19): 2340–7.Google Scholar
Arber, DA, Orazi, A, Hasserjian, R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.Google Scholar
Smit, CG, Meyler, L. Acute myeloid leukaemia after treatment with cytostatic agents. Lancet. 1970; 2(7674):671–2.Google Scholar
Churpek, JE. Familial myelodysplastic syndrome/acute myeloid leukemia. Best Pract Res Clin Haematol. 2017;30(4):287–9Google Scholar
Schwartz, JR, Ma, J, Lamprecht, T, et al. The genomic landscape of pediatric myelodysplastic syndromes. Nat Commun. 2017;8(1):1557.Google Scholar
Foucar, K, Langdon, RM, 2nd, Armitage, JO, Olson, DB, Carroll, TJ Jr. Myelodysplastic syndromes. A clinical and pathologic analysis of 109 cases. Cancer. 1985;56:553–61.Google Scholar
Koeffler, HP. Myelodysplastic syndromes (preleukemia). Semin Hematol. 1986;23:284–99.Google ScholarPubMed
Layton, DM, Mufti, GJ. Myelodysplastic syndromes: their history, evolution and relation to acute myeloid leukaemia. Blut. 1986;53:423–36.Google Scholar
Abel, GA, Efficace, F, Buckstein, RJ, et al. Prospective international validation of the Quality of Life in Myelodysplasia Scale (QUALMS). Haematologica. 2016;101(6):781.Google Scholar
Bejar, R, Steensma, DP. Recent developments in myelodysplastic syndromes. Blood. 2014;124(18):2793–803.CrossRefGoogle ScholarPubMed
Foucar, K, Langdon, RM 2nd, Armitage, JO, Olson, DB, Carroll, TJ Jr. Myelodysplastic syndromes. A clinical and pathologic analysis of 109 cases. Cancer. 1985;56(3):553.Google Scholar
Steensma, DP, Bejar, R, Jaiswal, S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126:9–16.Google Scholar
Gyan, E, Dreyfus, F, Fenaux, P. Refractory thrombocytopenia and neutropenia: a diagnostic challenge. Mediterr J Hematol Infect Dis. 2015;7:e2015018.Google Scholar
Bain, BJ. The bone marrow aspirate of healthy subjects. Br J Haematol. 1996;94(1):206–9.CrossRefGoogle ScholarPubMed
Matsuda, A, Germing, U, Jinnai, I, et al. Improvement of criteria for refractory cytopenia with multilineage dysplasia according to the WHO classification based on prognostic significance of morphological features in patients with refractory anemia according to the FAB classification. Leukemia. 2007;21(4):678–86.CrossRefGoogle Scholar
Della Porta, M, Travaglino, E, Boveri, E, et al. Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes. Leukemia. 2015;20(1):66–75.Google Scholar
Cazzola, M, Invernizzi, R, Begamaschi, G, et al. Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. Blood. 2003;101:1996–200.Google Scholar
Tricot, G, De Wolf-Peeters, C, Vlietinck, R, Verwilghen, RL. Bone marrow histology in myelodysplastic syndrome: prognostic value of abnormal localization of immature precursors in MDS. Br J Haematol. 1984;58:217–25.Google Scholar
Pagliuca, A, Layton, DM, Manoharan, A, et al. Myelofibrosis in primary myelodysplastic syndromes: a clinico-morphological study of 10 cases. Br J Haematol. 1989;71(4):499–504.Google Scholar
Lambertenghi-Deliliers, G, Orazi, A, Luksch, R, Annaloro, C, Soligo, D. Myelodysplastic syndrome with increased marrow fibrosis: a distinct clinico-pathological entity. Br J Haematol. 1991;78(2):161–6.CrossRefGoogle ScholarPubMed
Ohyashiki, K, Sasao, I, Ohyashiki, JH, et al. Clinical and cytogenetic characteristics of myelodysplastic syndromes developing myelofibrosis. Cancer. 1991;68(1):178–83.Google Scholar
Maschek, H, Georgii, A, Kaloutsi, V, et al. Myelofibrosis in primary myelodysplastic syndromes: a retrospective study of 352 patients. Eur J Haematol. 1992;48(4):208–14.Google Scholar
Wang, H, Wang, XQ, Xu, XP, Lin, GW. Bone marrow blasts level predicts prognosis in patients with refractory cytopenia with multilineage dysplasia. Eur J Haematol. 2009;83:550–8.Google Scholar
Mufti, GJ, Bennett, JM, Goasguen, J,et al; International Working Group on Morphology of Myelodysplastic Syndrome. Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts. Haematologica. 2008;93(11):1712–17.Google Scholar
Greenberg, PL, Tuechler, H, Schanz, J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454–65.Google Scholar
Senent, L, Arenillas, L, Luno, E, et al. Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes. Haematologica. 2013;98:568–75.Google Scholar
Font, P, Loscertales, J, Benavente, C, et al. Inter-observer variance with the diagnosis of myelodysplastic syndromes (MDS) following the 2008 WHO classification. Ann Hematol. 2013;92:19–24.Google Scholar
Font, P, Loscertales, J, Soto, C, et al. Inter-observer variance in myelodysplastic syndromes with less than 5% bone marrow blasts: unilineage vs. multilineage dysplasia and reproducibility of the threshold of 2% blasts. Ann Hematol. 2015;94:565–73.Google Scholar
Parmentier, S, Schetelig, J, Lorenz, K, et al. Assessment of dysplastic hematopoiesis: lessons from healthy bone marrow donors. Haematologica. 2012;97(5):723–30.Google Scholar
Wang, LJ, Glasser, L. Spurious dyserythropoiesis. Am J Clin Pathol. 2002;117:57–9.Google Scholar
Germing, U, Gattermann, N, Strupp, C, Aivado, M, Aul, C. Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res. 2000;24:983–92.Google Scholar
Gurney, M, Patnaik, MM, Hanson, CA, et al. The 2016 revised World Health Organization definition of ‘myelodysplastic syndrome with isolated del(5q)’; prognostic implications of single versus double cytogenetic abnormalities. Br J Haematol. 2017;178(1):57–60.Google Scholar
Geyer, JT, Verma, S, Mathew, S, et al. Bone marrow morphology predicts additional chromosomal abnormalities in patients with myelodysplastic syndrome with del(5q). Hum Pathol. 2013;44(3):346–56.Google Scholar
Valent, P, Orazi, A, Büsche, G, et al. Standards and impact of hematopathology in myelodysplastic syndromes (MDS). Oncotarget. 2010;1(7):483–96.Google Scholar
Niemeyer, CM, Baumann, I. Myelodysplastic syndrome in children and adolescents. Semin Hematol. 2008;45(1):60–70.Google Scholar
Strahm, B, Nöllke, P, Zecca, M,et al.; EWOG-MDS study group. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. Leukemia. 2011;25(3):455–62.Google Scholar
Forester, CM1, Sartain, SE, Guo, D, et al. Pediatric aplastic anemia and refractory cytopenia: A retrospective analysis assessing outcomes and histomorphologic predictors. Am J Hematol. 2015;90(4):320–6.CrossRefGoogle ScholarPubMed
van de Loosdrecht, AA, Alhan, C, Béné, MC, et al. Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes. Haematologica. 2009;94(8):1124–34.Google Scholar
Westers, TM, Ireland, R, Kern, W, et al. Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group. Leukemia. 2012;26(7):1730–41.Google Scholar
Alhan, C, Westers, TM, Cremers, EM, et al. High flow cytometric scores identify adverse prognostic subgroups within the revised international prognostic scoring system for myelodysplastic syndromes. Br J Haematol. 2014;167(1):100–9.Google Scholar
Sternberg, A, Killick, S, Littlewood, T, et al. Evidence for reduced B-cell progenitors in early (low-risk) myelodysplastic syndrome. Blood. 2005;106(9):2982–91.CrossRefGoogle ScholarPubMed
Maftoun-Banankhah, S, Maleki, A, Karandikar, NJ, et al. Multiparameter flow cytometric analysis reveals low percentage of bone marrow hematogones in myelodysplastic syndromes. Am J Clin Pathol. 2008;129(2):300–8.Google Scholar
Westers, TM, Ireland, R, Kern, W, et al. Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group. Leukemia. 2012;26(7):1730–41.Google Scholar
Della Porta, MG, Picone, C. Diagnostic utility of flow cytometry in myelodysplastic syndromes. Mediterr J Hematol Infect Dis. 2017;9(1):e2017017.Google Scholar
Kussick, SJ, Fromm, JR, Rossini, A, et al. Four-color flow cytometry shows strong concordance with bone marrow morphology and cytogenetics in the evaluation for myelodysplasia. Am J Clin Pathol. 2005;124:170–81.Google Scholar
Kern, W, Haferlach, C, Schnittger, S, Haferlach, T. Clinical utility of multiparameter flow cytometry in the diagnosis of 1013 patients with suspected myelodysplastic syndrome: correlation to cytomorphology, cytogenetics, and clinical data. Cancer. 2010;116:4549–63.Google Scholar
van de Loosdrecht, AA, Ireland, R, Kern, W, et al. Rationale for the clinical application of flow cytometry in patients with myelodysplastic syndromes: position paper of an International Consortium and the European LeukemiaNet Working Group. Leuk Lymphoma. 2012;54:472–5.Google Scholar
Wells, DA, Benesch, M, Loken, MR, et al. Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation. Blood. 2003;102:394–403.Google Scholar
Alhan, C, Westers, TM, van der Helm, LH, et al. Absence of aberrant myeloid progenitors by flow cytometry is associated with favorable response to azacitidine in higher risk myelodysplastic syndromes. Cytometry B Clin Cytom. 2014;86:207–15.Google Scholar
Westers, TM, Alhan, C, Chamuleau, ME, et al. Aberrant immunophenotype of blasts in myelodysplastic syndromes is a clinically relevant biomarker in predicting response to growth factor treatment. Blood. 2010;115:1779–84.Google Scholar
Ogata, K, Della Porta, MG, Malcovati, L, et al. Diagnostic utility of flow cytometry in low-grade myelodysplastic syndromes: a prospective validation study. Haematologica. 2009;94:1066–74.Google Scholar
Steensma, DP. Dysplasia has A differential diagnosis: distinguishing genuine myelodysplastic syndromes (MDS) from mimics, imitators, copycats and impostors. Curr Hematol Malig Rep. 2012;7(4):310–20.Google Scholar
Ramadurai, J, Shapiro, C, Kozloff, M, Telfer, M. Zinc abuse and sideroblastic anemia. Am J Hematol. 1993;42(2):227–8.Google Scholar
Gregg, XT, Reddy, V, Prchal, JT. Copper deficiency masquerading as myelodysplastic syndrome. Blood. 2002;100(4):1493–5.Google Scholar
Latvala, J, Parkkila, S, Niemela, O. Excess alcohol consumption is common in patients with cytopenia: studies in blood and bone marrow cells. Alcohol Clin Exp Res. 2004;28(4):619–24.Google Scholar
Ballard, HS. The hematological complications of alcoholism. Alcohol Health Res World. 1997;21(1):42–52.Google Scholar
Ohba, R, Furuyama, K, Yoshida, K, et al. Clinical and genetic characteristics of congenital sideroblastic anemia: comparison with myelodysplastic syndrome with ring sideroblast (MDS-RS). Ann Hematol. 2013;92(1):1–9.Google Scholar
Scott, CL, Robb, L, Papaevangeliou, B, et al. Reassessment of interactions between hematopoietic receptors using common beta-chain and interleukin-3-specific receptor beta-chain-null cells: no evidence of functional interactions with receptors for erythropoietin, granulocyte colony-stimulating factor, or stem cell factor. Blood. 2000;96(4):1588–90.Google Scholar
Valent, P, Orazi, A, Steensma, DP, et al. Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions. Oncotarget. 2017;8(43):73,483–500.Google Scholar
Steensma, DP, Bejar, R, Jaiswal, S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9–16.Google Scholar
Jaiswal, S, Natarajan, P, Silver, AJ, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377(2):111–21.Google Scholar
Valent, P, Bain, BJ, Bennett, JM, et al. Idiopathic cytopenia of undetermined significance (ICUS) and idiopathic dysplasia of uncertain significance (IDUS), and their distinction from low risk MDS. Leuk Res. 2012;36(1):1–5.Google Scholar
Valent, P, Jäger, E, Mitterbauer-Hohendanner, G, et al. Idiopathic bone marrow dysplasia of unknown significance (IDUS): definition, pathogenesis, follow up, and prognosis. Am J Cancer Res. 2011;1:531–41.Google ScholarPubMed
Tiacci, E, Trifonov, V, Schiavoni, G, et al. BRAF mutations in hairy-cell leukemia. N Engl J Med. 2011;364(24):2305–15.Google Scholar
Rajala, HL, Eldfors, S, Kuusanmäki, H, et al. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood. 2013;121(22):4541–50.Google Scholar
Dal Cin, P, Aster, JC, DeAngelo, DJ. When to go FISHing. Am J Clin Pathol. 2010;133(3):351–3.Google Scholar
Schanz, J, Tuchler, H, Sole, F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol 2012;30:820−9.Google Scholar
Giagounidis, AA, Germing, U, Strupp, C, et al. Prognosis of patients with del(5q) MDS and complex karyotype and the possible role of lenalidomide in this patient subgroup. Ann Hematol. 2005;84(9):569–71.Google Scholar
Jerez, A, Gondek, LP, Jankowska, AM, et al. Topography, clinical, and genomic correlates of 5q myeloid malignancies revisited. J Clin Oncol. 2012;30(12):1343–9.Google Scholar
Haase, D, Germing, U, Schanz, J, et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood. 2007;110(13):4385–95.Google Scholar
Schanz, J, Tüchler, H, Solé, F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012;30(8):820–9.Google Scholar
Schanz, J, Steidl, C, Fonatsch, C, et al. Coalesced multicentric analysis of 2,351 patients with myelodysplastic syndromes indicates an underestimation of poor-risk cytogenetics of myelodysplastic syndromes in the international prognostic scoring system. J Clin Oncol. 2011;29(15):1963–70.Google Scholar
Solé, F, Espinet, B, Sanz, GF, et al. Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Español de Citogenética Hematológica. Br J Haematol. 2000;108(2):346–56.Google Scholar
Della Porta, MG, Travaglino, E, Boveri, E, et al.; Rete Ematologica Lombarda (REL) Clinical Network. Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes. Leukemia. 2015;29(1):66–75.Google Scholar
Bejar, R. Clinical and genetic predictors of prognosis in myelodysplastic syndromes. Haematologica. 2014;99:956–64.Google Scholar
Bejar, R, Stevenson, K, Abdel-Wahab, O, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364:2496–506.Google Scholar
Sperling, SA, Gibson, CJ, Ebert, BL. The genetics of myelodysplastic syndrome: from clonal hematopoiesis to secondary leukemia. Nat Rev Cancer. 2017; 17(1): 5–19.Google Scholar
West, AH, Godley, LA, Churpek, JE. Familial myelodysplastic syndrome/acute leukemia syndromes: a review and utility for translational investigations. Ann N Y Acad Sci. 2014;1310:111–18.Google Scholar
Zatterale, A, Calzone, R, Renda, S, et al. Identification and treatment of late onset Fanconi's anemia. Haematologica. 1995;80(6):535–8.Google ScholarPubMed
Link, DC, Schuettpelz, LG, Shen, D, et al. Identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML. JAMA. 2011;305(15):1568–76.CrossRefGoogle ScholarPubMed
Gangat, N, Patnaik, MM, Tefferi, A. Myelodysplastic syndromes: contemporary review and how we treat. Am J Hematol. 2016;91(1):76–89.CrossRefGoogle ScholarPubMed
Fenaux, P, Mufti, GJ, Hellstrom-Lindberg, E, et al.; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223–32.CrossRefGoogle Scholar
Kantarjian, H, Issa, JP, Rosenfeld, CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006;106(8):1794–803.Google Scholar
List, A, Kurtin, S, Roe, DJ, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005;352(6):549–57.Google Scholar
Silverman, LR, Demakos, EP, Peterson, BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002;20(10):2429–40.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×