What are the symptoms and management of Myelodysplastic Syndromes (MDS)?

Symptoms and Management of Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes (MDS) primarily present with symptoms related to blood cytopenias, including fatigue from anemia, infections due to neutropenia, and bleeding from thrombocytopenia, with treatment based on risk stratification using the IPSS-R system. 1, 2

Clinical Presentation

Common Symptoms

• Anemia-related symptoms (most common presentation):

  • Fatigue
  • Weakness
  • Pallor
  • Dyspnea on exertion
  • Palpitations

• Neutropenia-related symptoms:

  • Recurrent or persistent infections
  • Fever

• Thrombocytopenia-related symptoms:

  • Easy bruising
  • Petechiae
  • Bleeding (gums, nose, gastrointestinal)
  • Excessive bleeding from minor injuries

Laboratory Findings

• Peripheral blood abnormalities 1:

  • Cytopenias (usually macrocytic anemia)
  • Dysplastic features in blood cells:
    • Granulocytes: Pseudo Pelger-Huet cells, abnormal chromatin clumping, hypo-/degranulation
    • Platelets: Giant platelets, anisometry
    • Red cells: Anisocytosis, poikilocytosis, dimorphic erythrocytes, tear drop cells

• Bone marrow findings 1:

  • Typically hypercellular (occasionally hypocellular)
  • Dysplastic features in ≥10% of cells in one or more lineages
  • Increased blast percentage (variable)
  • Ring sideroblasts (in some subtypes)

Diagnosis

Diagnosis requires:

1. Persistent cytopenias (≥4 months)
2. Exclusion of other causes of cytopenias
3. Presence of dysplastic features in bone marrow
4. Cytogenetic or molecular genetic abnormalities (in many cases)

Essential diagnostic tests 1:

• Complete blood count with differential
• Peripheral blood smear examination
• Bone marrow aspiration and biopsy with cytogenetics
• Iron staining (Perls stain) to identify ring sideroblasts
• Molecular testing for genetic mutations

Risk Stratification

Risk assessment using the Revised International Prognostic Scoring System (IPSS-R) 2:

• Considers:
  • Cytogenetic abnormalities
  • Bone marrow blast percentage
  • Hemoglobin level
  • Platelet count
  • Absolute neutrophil count

Risk categories:

• Lower-risk: Very low, low, and some intermediate
• Higher-risk: Some intermediate, high, and very high

Management

Lower-Risk MDS

1. Anemia management 2:

   • Erythropoiesis-stimulating agents (ESAs) for patients with serum erythropoietin <500 U/L
   • Response rate: 40-60%
   • Responses typically occur within 8-12 weeks

2. For del(5q) patients 2:

   • Lenalidomide 10 mg/day for 3 weeks every 4 weeks
   • Response rate: 60-65% achieve transfusion independence
   • Median duration of response: 2-2.5 years

3. For patients with ring sideroblasts or SF3B1 mutation 2:

   • Luspatercept (especially after ESA failure)

4. After ESA failure (non-del(5q)) 2:

   • Antithymocyte globulin ± cyclosporine (especially in younger patients)
   • Hypomethylating agents (azacitidine, decitabine)
   • Lenalidomide (transfusion independence rate: 25-30%)

Higher-Risk MDS

1. For eligible patients ≤70 years 2:

   • Allogeneic hematopoietic stem cell transplantation (only potentially curative option)
   • Hypomethylating agents can be used as a bridge to transplant

2. For patients >70 years or not eligible for transplantation 2, 3:

   • Azacitidine 75 mg/m²/day subcutaneously for 7 days every 28 days
   • Decitabine 15 mg/m² IV every 8 hours for 3 days every 6 weeks
   • Continue for at least 6 cycles before assessing efficacy

Supportive Care

1. Transfusion support 2:

   • RBC transfusions for symptomatic anemia
   • Platelet transfusions for severe thrombocytopenia or bleeding

2. Iron chelation therapy 2:

   • For heavily transfused patients at risk of iron overload
   • Monitor iron status in transfusion-dependent patients

3. Infection management 2:

   • Broad-spectrum antibiotics for infections
   • Consider short-term G-CSF during severe infections

Monitoring and Follow-Up

• Regular complete blood counts to assess disease stability 2
• Monitor for treatment-related toxicities
• Repeat bone marrow examinations as clinically indicated
• Assess for disease progression to acute myeloid leukemia (occurs in approximately one-third of cases) 1

Prognosis

• Lower-risk MDS: Median survival approximately 3-10 years 4
• Higher-risk MDS: Median survival less than 3 years 4
• Overall 5-year survival rate: approximately 37% 4

Important Considerations

• MDS is primarily a disease of the elderly (median age ~70 years) 1
• Secondary MDS (therapy-related) generally has poorer prognosis 1
• TP53 mutations in lower-risk MDS with del(5q) confer resistance to lenalidomide and higher risk of AML progression 2
• Response to hypomethylating agents may take time - at least 6 cycles are recommended before assessing efficacy 2

Remember that early diagnosis and risk-appropriate management are crucial for improving outcomes and quality of life in patients with MDS.