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).
Primary MDS (90% of cases) 
- Most commonly manifests in older adults 
- Idiopathic: likely due to spontaneous mutations 
- Secondary MDS (10% of cases): due to exogenous bone marrow damage 
|Classifications of MDS |
|2022 World Health Organization (WHO) 5th edition|| |
|2022 International Consensus Classification (ICC)|
In a previous WHO classification system, refractory anemia was a subtype of MDS. 
- Asymptomatic in 20% of cases
- Depending on the affected cell line: 
- Hepatosplenomegaly (uncommon)
- Obtain initial studies, including workup for other causes of cytopenia and dysplasia.
- If the cause is still unexplained, refer to hematology-oncology for:
- Advanced diagnostic studies (i.e., bone marrow and genetic studies)
- Confirmation of diagnosis and classification of MDS, based on the presence of ≥ 1 of the following: 
MDS is often identified during evaluation for unexplained cytopenia.
Initial studies 
- CBC with peripheral smear: will show myeloid cell line abnormalities in MDS
- Studies to exclude other causes of cytopenia and/or dysplasia
- Possible additional studies: may show nonspecific abnormalities 
Advanced studies for MDS 
- Bone marrow studies (aspiration and/or biopsy): to evaluate for myeloid cell line abnormalities in MDS
- Genetic evaluation 
Overview of hematological findings in MDS 
|Myeloid cell line abnormalities in MDS |
|Peripheral smear||Bone marrow studies|
|Cell count || |
|Thrombocyte lineage|| |
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). 
Other causes of cytopenia and/or dysplasia include: 
- Nonmalignant causes
- Deficiencies in micronutrients (e.g., B6, B12, folate, copper, iron) 
- Medications 
- Reactive changes due to acute viral illnesses
- Chronic alcohol consumption
- Infectious diseases (e.g., HIV, CMV, TB)
- Autoimmune diseases (e.g., SLE, rheumatoid arthritis)
- Chronic kidney disease
- Chronic liver disease
- Other hematological conditions 
- Other malignancies associated with cytopenias
The differential diagnoses listed here are not exhaustive.
Refer all patients to hematology-oncology for management.
- All patients
- Assess for comorbidities and discuss goals of care.
- Use scoring systems for risk stratification in MDS.
- Provide supportive therapy for symptomatic and/or significant cytopenia(s).
- Offer enrollment in clinical trials.
- Monitor regularly for treatment response and disease progression.
- Identify and treat complications (e.g., iron overload, infections, bleeding).
- High-risk MDS
- Low-risk MDS: Screen for indications for pharmacotherapy for MDS.
Allogeneic stem cell transplantation is the only curative option for MDS.
Risk stratification in MDS 
- To determine treatment, patients with MDS are categorized as having either low-risk or high-risk MDS.
- Clinical scoring systems include:
- Common high-risk features:
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 
- Neutropenia: recombinant (G-CSF) may be used in select cases 
- Thrombocytopenia: platelet transfusions 
- Iron overload: Provide iron chelation (e.g., deferasirox) to transfusion-dependent patients with elevated ferritin levels. 
- See also “Anticancer treatment-related complications” in “Principles of cancer care.”
Pharmacotherapy for MDS 
- Pharmacotherapy is noncurative but aims to:
|MDS treatment by risk stratification |
|Lower-risk MDS|| |
Inadequate response to hypomethylating agents is associated with a poor prognosis.