Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a group of clonal neoplasms with maturation defects characterized by dysplasia, cytopenia, and immature bone marrow precursors. Myelodysplastic syndromes can be idiopathic, or secondary to various injurious exposures such as cytotoxic chemotherapy, ionizing radiation, or environmental toxins. The median patient age is 70 years old. Presentation includes symptoms of anemia (fatigue), neutropenia (infection), or thrombocytopenia (bleeding). The diagnosis is based on bone marrow evaluation, which reveals cytopenia, dysplasia in at least 1 lineage, and blast cells in < 20% of marrow cellularity. Cytogenetic and molecular studies are required for classification, prognosis, and therapy-related decisions. An increased cumulative risk of transformation to AML is present and varies depending on MDS subtype. Management includes supportive care, use of hematopoietic growth factors, immunosuppressive therapy, and allogeneic hematopoietic cell transplantation.

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Myelodysplastic syndromes (MDS) are clonal, bone marrow diseases characterized by the presence of dysplastic, immature, bone marrow precursors and peripheral cytopenias.


  • Incidence increases significantly with age.
  • Median age of presentation: approximately 70 years old
  • Annual incidence in the United States:
    • 1–5 cases per 100,000
    • Individuals > 70 years of age: 20 cases per 100,000
  • Men > women


  • Primary or idiopathic
  • Secondary (exposure to sources leading to chromosomal damage):
    • Postcancer treatment with alkylating agents (with or without radiotherapy)
    • Prior treatment with topoisomerase II inhibitors (anthracycline or etoposide)
    • Prior exposure to certain chemicals:
      • Benzene
      • Insecticides, weed killers, fungicides
      • Tobacco
    • Inherited genetic abnormalities (e.g., trisomy 21, trisomy 8, Fanconi anemia, ataxia-telangiectasia) 
    • Clonal hematopoiesis of indeterminate potential 
    • Hematologic conditions (e.g., aplastic anemia, polycythemia vera, paroxysmal nocturnal hemoglobinuria, congenital neutropenia) 
    • Familial predisposition (congenital platelet disorders)


The majority of MDS is attributed to chromosomal deletions and translocations, or gene mutations.

  • Chromosomal abnormalities:
    • Deletion of chromosome 5 (del(5q)): 
      • Most common (15% of cases)
      • Women > men
      • Anemia with normal or ↑ platelets
    • Chromosome 7 involvement:
      • Monosomy 7 (-7) or deletion of chromosome 7 (del(7q)) long arm: 
      • 10% of patients with de novo MDS
    • Trisomy 8: < 10% of patients
    • Deletion of chromosome 20 (del(20q)): < 5% of cases
    • Loss of Y chromosome
  • Gene mutations:
    • Affected genes are involved in:
      • Messenger RNA (mRNA) splicing
      • DNA methylation
      • Chromatin modification
      • Transcription factors (loss-of-function mutation of RUNX1)
    • Loss-of-function mutation in TP53 (< 10% of cases)

Clinical Presentation

  • Anemia (most common):
    • Fatigue
    • Dyspnea
    • Tachycardia or signs of congestive heart failure 
  • Leukopenia (↓ WBC, WBC dysfunction): 
    • Fever
    • Recurrent bacterial infection (skin most affected)
  • Thrombocytopenia: 
    • Easy bruising
    • Gingival bleeding
    • Petechiae
  • Symptoms of autoimmune disease: approximately 25% of patients (e.g., rheumatoid arthritis, psoriasis)
  • Acquired α-thalassemia (due to abnormal presence of hemoglobin H)
  • Skin disease: Sweet syndrome (acute febrile neutrophilic dermatosis)
Sweet syndrome

Sweet syndrome: painful, erythematous, pseudovascular plaques of acute febrile neutrophilic dermatosis

Image: “Sweet’s syndrome–a comprehensive review of an acute febrile neutrophilic dermatosis” by Cohen PR. License: CC BY 2.0


Diagnostic characteristics

  • Cytopenia in at least 1 blood lineage
  • ≥ 10% of nucleated cells with dysplasia (disordered differentiation) in at least 1 lineage
  • < 20% blasts in blood and bone marrow
  • Characteristic cytogenetic or molecular findings
  • No evidence of an alternate cause

Diagnostic evaluation

  • History:
    • Alcohol and drug use
    • Medications
    • Exposure to toxic chemicals
    • Prior chemotherapy or exposure to radiation
  • CBC:
    • Macrocytic anemia: ↑ MCV, ↓ Hb
    • Thrombocytopenia: ↓ platelets
    • Leukopenia: ↓ WBC
    • Circulating immature neutrophils: myelocytes, promyelocytes, myeloblasts
  • Peripheral blood smear:
    • RBCs: macrocytes, ringed sideroblasts, irregularly-shaped cells
    • WBCs: dysplastic, hyposegmented neutrophils (pseudo–Pelger-Huët abnormality)
    • Platelets: thrombocytopenia
  • Bone marrow biopsy (Wright-Giemsa and iron stains):
    • Hypercellular bone marrow
    • Dysplastic cells in 1 or more lineages
    • Increased myeloblasts (< 20% to differentiate from AML)
    • Ringed sideroblasts
    • Myelofibrosis of various degrees
  • Bone marrow karyotype
  • Cytogenetic analysis:
    • Gene microarray studies for genomic abnormalities
    • FISH for chromosomal abnormalities
    • PCR for gene rearrangements


After MDS confirmation, patients are categorized based on the 2016 WHO classification, which is important for treatment selection and prognosis determination.

Classification is based on:

  • Dysplastic lineage(s)
  • Number of cytopenias:
    • Anemia: Hb < 10 g/dL
    • Leukopenia: absolute neutrophil count < 1.8 × 10⁹/L
    • Thrombocytopenia: platelet count < 100 × 10⁹/L
  • Percentage of blasts in the blood and bone marrow
  • Percentage of ring sideroblasts
  • Cytogenetic findings


  • < 5% blasts in the bone marrow:
    • MDS with single lineage dysplasia (SLD)
    • MDS with multiple lineage dysplasia (MLD)
    • MDS with ringed sideroblasts-SLD (sideroblasts ≥ 15%)
    • MDS with ringed sideroblasts-MLD (sideroblasts ≥ 15%)
    • MDS with isolated del(5q)
  • 5%–19% blasts in the bone marrow:
    • MDS with excess blasts (EB)-1: 5%–9% blasts
    • MDS with EB-2: 10%–19% blasts
  • MDS unclassifiable


Management approach

  • Dependent on clinical presentation and comorbidities
  • Determine risk stratus (lower risk vs. higher risk) based on prognostic variables with higher risk for the following:
    • Bone marrow blasts: > 5%
    • Cytopenias: 2 or 3
    • Cytogenetics: Certain mutations (e.g., -7 or del(7q)) have a poorer prognosis.
    • Higher risk group:
      • Prognosis is worse.
      • Higher incidence of transformation to AML
  • Determine physiological fitness: 
    • Presence of comorbid diseases 
    • Physical performance tests: ability to perform activities of daily living (ADLs)
    • Cognition
  • Determine goals of care:
    • Cure is rarely feasible.
    • Discuss personal preferences and values.
    • Goals: 
      • ↓ Symptoms and provide comfort.
      • Prolong survival.
      • Enhance the quality of life.
      • Minimize therapy-related toxicity.

Management options

  • Observation: lower-risk, asymptomatic patients
  • Low-intensity therapy:
    • Erythropoiesis/myelopoiesis stimulating factors (e.g., erythropoietin) 
    • Del(5q): lenalidomide 
    • RBC/platelet transfusion as needed
    • Hypomethylating agents (e.g., azacitidine, decitabine) 
  • High-intensity therapy:
    • Chemotherapy (e.g., cytarabine + anthracycline)
    • Allogeneic hematopoietic cell transplantation (HCT) for young and medically-fit patients
    • Targeted therapy for specific mutations

Differential Diagnosis

  • Isolated cytopenias: defects in 1 cell line (isolated anemia, leukopenia, or thrombocytopenia). Evaluation requires a detailed medical history: dietary practices (e.g., folate, vitamin B12, and/or copper deficiency), travel (e.g., acquired parasitic infection), chronic blood loss, medications, alcohol consumption, toxic exposures, chronicity of cytopenia, family history, and GI, autoimmune, or neoplastic disorders. In most cases, diagnosis is established with history, peripheral smear, and bone marrow biopsy (if needed). 
  • Primary myelofibrosis: a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis and extramedullary hematopoiesis in the spleen and liver. The abnormality stems from genetic mutations of hematopoietic stem cells (JAK2, CALR, or MPL mutation). Clinical findings are fatigue, splenomegaly, hepatomegaly, and anemia. Peripheral smear shows leukoerythroblastosis and contains precursors of WBCs, RBCs, nucleated RBCs, and teardrop cells. Diagnosis is made by bone marrow examination and molecular testing. Management includes allogeneic HCT and medication (ruxolitinib and fedratinib).
  • Acute myeloid leukemia (AML): the malignant and uncontrolled proliferation of myeloid precursors, resulting in cytopenias and increased numbers (> 20%) of immature myelocytes (i.e., blasts) in the peripheral circulation and bone marrow. The finding of Auer rods (linear inclusions in the cytoplasm of blast cells) is pathognomonic of AML. Leukemic cells can infiltrate various organs, causing organomegaly and neurologic sequelae. Patients with MDS are at high risk of transformation to AML.
  • Chronic myelomonocytic leukemia (CMML): a rare myelodysplastic/myeloproliferative neoplasm with increased production of maturing monocytic cells and, sometimes, dysplastic neutrophils. Chronic myelomonocytic leukemia is often accompanied by constitutional symptoms, splenomegaly, anemia, and/or thrombocytopenia. The bone marrow morphology shows prominent dysplasia in at least 2 of the 3 myeloid lineages. Management is supportive care, hydroxyurea, a hypomethylating agent, and allogeneic HCT.


  1. Aster, J.C., Stone, R.M. (2021). Clinical manifestations and diagnosis of myelodysplastic syndromes (MDS). UpToDate. Retrieved April 26, 2021, from
  2. Besa, E.C. (2021). Myelodysplastic Syndrome (MDS). Medscape. Retrieved April 26, 2021, from
  3. Estey, E.H., Negrin, R.S. (2021). Treatment of high or very high risk myelodysplastic syndromes. UpToDate. Retrieved April 26, 2021, from
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  5. Hasserjian, R.P. (2019). Myelodysplastic Syndrome Updated. Pathobiology. 86(1),7–13.

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