Myelodysplastic syndromes

Last updated: October 25, 2023

Summarytoggle arrow icon

Myelodysplastic syndromes (MDSs) are a group of clonal hematopoietic stem cell neoplasms characterized by impaired proliferation and differentiation of myeloid stem cells within the bone marrow. Primary (idiopathic) MDS, likely related to spontaneous mutations, is most common; secondary MDS may result from inciting events such as exposure to chemotherapy. MDS is typically seen in older adults and is evidenced by laboratory abnormalities, symptoms of cytopenia(s), and findings of extramedullary hematopoiesis. To diagnose and classify MDS, other causes of cytopenia and/or dysplasia must be excluded and bone marrow and genetic studies should be conducted. These studies typically show dysplasia and cytopenia in at least one mature myeloid cell line on CBC, bone marrow hypercellularity of myeloid precursors, and MDS-associated genetic abnormalities. All patients should receive supportive therapy as needed, including transfusions and treatment of associated iron overload. Additional treatment is guided by risk stratification in MDS. Individuals with high-risk disease are treated with hypomethylating agents and possibly intensive chemotherapy; they should also all be assessed for fitness for allogeneic hematopoietic stem cell transplantation, which is the only curative option. Treatment options for individuals with low-risk disease include expectant management, hypomethylating agents, and drugs such as lenalidomide. Close surveillance is required to determine treatment response and monitor for disease progression (e.g., to acute myelogenous leukemia or bone marrow failure).

Etiologytoggle arrow icon

Classificationtoggle arrow icon

Classifications of MDS [3][4]
2022 World Health Organization (WHO) 5th edition
  • MDS with defining genetic abnormalities
    • MDS with low blasts and isolated 5q deletion (MDS-5q)
    • MDS with low blasts and either SF3B1 mutation (MDS-SF3B1) OR ≥ 15% ring sideroblasts
    • MDS with biallelic TP53 inactivation (MDS-biTP53)
  • MDS, morphologically defined
    • MDS with low blasts (MDS-LB)
    • MDS, hypoplastic (MDS-h) [3]
    • MDS with increased blasts (MDS-IB) [3]
2022 International Consensus Classification (ICC)
  • Lower-risk: MDS without excess blasts
    • MDS with mutated SF3B1 (MDS-SF3B1)
    • MDS with del(5q) [MDS-del(5q)]
    • MDS, NOS
  • Higher risk
    • MDS with excess blasts (MDS-EB) [4]
    • MDS with mutated TP53
    • MDS/AML

MDS and AML are differentiated based on the number of myeloblasts in bone marrow or peripheral blood cells: < 20% in MDS and ≥ 20% in AML. [3][4]

In a previous WHO classification system, refractory anemia was a subtype of MDS. [5]

Clinical featurestoggle arrow icon

Diagnosticstoggle arrow icon

Approach [7][8][9]

Workup for MDS may be prompted by symptoms related to cytopenias or by the discovery of incidental cytopenia.

MDS is often identified during evaluation for unexplained cytopenia.

Initial studies [7][8][10]

Advanced studies for MDS [3][7][12]

Genetic evaluation is required for classification of MDS, as well as for risk-stratification of patients to estimate prognosis and guide treatment. [3][7]

Overview of hematological findings in MDS [12][14][15]

Myeloid cell line abnormalities in MDS [12][14][15]
Peripheral smear Bone marrow studies
Cell count [12]
Dysplasias Erythrocyte lineage
Leukocyte lineage
Thrombocyte lineage

Anemia is the most common cytopenia in MDS, and may manifest as macrocytic anemia or normocytic anemia. [9]

The pseudo-Pelger-Huet anomaly is also seen in patients receiving certain medications (e.g., chemotherapy, transplant medications) and in other hematological disorders (e.g., myeloproliferative disorders). [16][17]

Differential diagnosestoggle arrow icon

Other causes of cytopenia and/or dysplasia include: [7][8][10]

Precursor clonal hematopoietic conditions can progress to MDS. MDS can itself progress to acute myeloid leukemia. [4][13]

The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

Approach [7][10][13]

Refer all patients to hematology-oncology for management.

Allogeneic stem cell transplantation is the only curative option for MDS.

Risk stratification in MDS [7][10][13]

  • To determine treatment, patients with MDS are categorized as having either low-risk or high-risk MDS.
  • Clinical scoring systems include:
    • Revised International Prognostic Scoring System (IPSS-R)
    • Molecular International Prognostic Scoring System (IPSS-M) [19][20]
  • Common high-risk features:
    • Patient > 60 years of age [10]
    • Significant or multiple cytopenias
    • Increased myeloblasts (≥ 5%) in the bone marrow
    • Multiple and/or unfavorable genetic abnormalities

Patients with a high-risk feature may still have low-risk MDS if the total prognostic score is below the cutoff value for high-risk MDS.

Supportive therapy [7][10][13]

Disease-related cytopenias

Treatment-associated complications

Pharmacotherapy for MDS [7][10][13]

  • Pharmacotherapy is noncurative but aims to:
    • Increase cell counts
    • Improve symptoms and quality of life
    • Reduce transfusion burden
    • Delay progression to AML
MDS treatment by risk stratification [7][13]
Indications Treatment
Higher-risk MDS
Lower-risk MDS
  • Luspatercept
  • Multiple (multilinear) cytopenias
  • Failure of supportive therapy alone (e.g., transfusion-dependent patients)

Lenalidomide may cause significant neutropenia and thrombocytopenia. [7]

Inadequate response to hypomethylating agents is associated with a poor prognosis. [13]

Complicationstoggle arrow icon

We list the most important complications. The selection is not exhaustive.

Referencestoggle arrow icon

  1. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022; 36 (7): p.1703-1719.doi: 10.1038/s41375-022-01613-1 . | Open in Read by QxMD
  2. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022; 140 (11): p.1200-1228.doi: 10.1182/blood.2022015850 . | Open in Read by QxMD
  3. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009; 114 (5): p.937-951.doi: 10.1182/blood-2009-03-209262 . | Open in Read by QxMD
  4. Steensma DP. Myelodysplastic Syndromes. Mayo Clinic Proceedings. 2015; 90 (7): p.969-983.doi: 10.1016/j.mayocp.2015.04.001 . | Open in Read by QxMD
  5. Lopez Rubio M, Anna Gaya A, Morado M, Carrasco V, Gonzalez Fernandez A, Villegas A. Relationship between myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria: Spanish Erythropathology Group and Spanish Paroxysmal Nocturnal Hemoglobinuria Working Group Experience. Blood. 2015; 126: p.4546.
  6. Aster JC, Stone RM, Larson A, Rosmarin AG. Clinical Manifestations and Diagnosis of the Myelodysplastic Syndromes . In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: November 30, 2016. Accessed: September 7, 2017.
  7. Sekeres MA, Taylor J. Diagnosis and Treatment of Myelodysplastic Syndromes. JAMA. 2022; 328 (9): p.872.doi: 10.1001/jama.2022.14578 . | Open in Read by QxMD
  8. 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): p.73483-73500.doi: 10.18632/oncotarget.19008 . | Open in Read by QxMD
  9. Caligiuri M, Levi MM, Kaushansky K, et al. Williams Hematology, 9E. McGraw-Hill Education / Medical ; 2015
  10. Fenaux P, Haase D, Santini V, Sanz GF, Platzbecker U, Mey U. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021; 32 (2): p.142-156.doi: 10.1016/j.annonc.2020.11.002 . | Open in Read by QxMD
  11. Gattermann N. Iron overload in myelodysplastic syndromes (MDS). Int J Hematol. 2018; 107 (1): p.55-63.doi: 10.1007/s12185-017-2367-1 . | Open in Read by QxMD
  12. Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2). McGraw-Hill Education / Medical ; 2018
  13. Garcia‐Manero G. Myelodysplastic syndromes: 2023 update on diagnosis, risk‐stratification, and management. Am J Hematol. 2023; 98 (8): p.1307-1325.doi: 10.1002/ajh.26984 . | Open in Read by QxMD
  14. Sanz-De Pedro M, Wang W, Kanagal-Shamanna R, Khoury JD. Myelodysplastic Syndromes: Laboratory Workup in the Context of New Concepts and Classification Criteria. Curr Hematol Malig Rep. 2018; 13 (6): p.467-476.doi: 10.1007/s11899-018-0483-5 . | Open in Read by QxMD
  15. Myelodysplastic syndromes. Updated: August 1, 2015. Accessed: April 13, 2017.
  16. Wang E, Boswell E, Siddiqi I, et al. Pseudo–Pelger-Huët Anomaly Induced by Medications. Am J Clin Pathol. 2011; 135 (2): p.291-303.doi: 10.1309/ajcpvfy95maobkrs . | Open in Read by QxMD
  17. Abramson, Neil. Pelger-Huet anomaly and pseudo (acquired) Pelger-Huet. Blood. 2006; 107 (9): p.3428-3428.doi: 10.1182/blood.v107.9.3428.3428 . | Open in Read by QxMD
  18. Bernard E, Tuechler H, Greenberg PL, et al. Molecular International Prognostic Scoring System for Myelodysplastic Syndromes. NEJM Evid. 2022; 1 (7).doi: 10.1056/evidoa2200008 . | Open in Read by QxMD
  19. Aguirre LE, Al Ali N, Sallman DA, et al. Assessment and validation of the molecular international prognostic scoring system for myelodysplastic syndromes. Leukemia. 2023; 37 (7): p.1530-1539.doi: 10.1038/s41375-023-01910-3 . | Open in Read by QxMD
  20. Rollison DE, Shain KH, Lee J-H, et al. Subsequent primary malignancies and acute myelogenous leukemia transformation among myelodysplastic syndrome patients treated with or without lenalidomide. Cancer Med. 2016; 5 (7): p.1694-1701.doi: 10.1002/cam4.721 . | Open in Read by QxMD
  21. Mintzer DM, Billet SN, Chmielewski L. Drug-Induced Hematologic Syndromes. Advances in Hematology. 2009; 2009: p.1-11.doi: 10.1155/2009/495863 . | Open in Read by QxMD
  22. Types of Myelodysplastic Syndromes. Updated: July 2, 2015. Accessed: April 13, 2017.

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