What is the initial approach for managing myelodysplastic syndrome (MDS)?

Initial Management of Myelodysplastic Syndrome (MDS)

The initial approach to managing myelodysplastic syndrome should involve risk stratification using the International Prognostic Scoring System (IPSS) or revised IPSS (IPSS-R), followed by supportive care for all patients and risk-adapted therapy based on lower-risk versus higher-risk disease classification. 1

Risk Stratification

Risk stratification is the critical first step in MDS management:

• Use IPSS or IPSS-R to categorize patients into:

  • Lower-risk: IPSS low/INT-1 or IPSS-R very low/low/intermediate
  • Higher-risk: IPSS INT-2/high or IPSS-R intermediate/high/very high 2, 1

• Additional factors to consider:

  • Age and performance status
  • Presence of comorbidities
  • Stability of blood counts over time
  • Cytogenetic abnormalities
  • Molecular mutations (especially TP53 and SF3B1) 1

Supportive Care (For All Patients)

All MDS patients should receive appropriate supportive care regardless of risk category:

• Transfusion support:

  • RBC transfusions for symptomatic anemia (generally leukocyte-reduced)
  • Platelet transfusions for severe thrombocytopenia or bleeding 2

• Infection management:

  • Broad-spectrum antibiotics for fever or infection
  • Consider short-term G-CSF during severe infections 1
  • Aminocaproic acid may be considered for bleeding refractory to platelet transfusions 2

• Psychosocial support:

  • Quality-of-life assessment addressing physical, functional, emotional, spiritual, and social domains 2
  • Connection with patient support groups 1

Lower-Risk MDS Management

For patients with lower-risk disease (IPSS low/INT-1), the therapeutic goal is hematologic improvement:

1. For anemia with serum erythropoietin <500 U/L:

   • Erythropoiesis-stimulating agents (ESAs) ± G-CSF as first-line treatment
   • Response rates: 40-60% with responses typically within 8-12 weeks 1

2. For MDS with del(5q):

   • Lenalidomide is the preferred treatment
   • Response rate: 60-65% achieve transfusion independence 1

3. For MDS with ring sideroblasts or SF3B1 mutation:

   • Consider luspatercept 1

4. For patients with immunologically mediated myelosuppression:

   • Consider immunosuppressive therapy (antithymocyte globulin or cyclosporin A) 3

Higher-Risk MDS Management

For patients with higher-risk disease (IPSS INT-2/high), the goal is to alter disease natural history and prolong survival:

1. Evaluate for allogeneic hematopoietic stem cell transplantation (allo-HSCT):

   • Consider for eligible patients ≤70 years as it's the only potentially curative option 1

2. For patients ineligible for transplantation:

   • Hypomethylating agents (HMAs) are standard of care:
     • Azacitidine: 75 mg/m²/day subcutaneously for 7 days every 28 days, minimum 6 cycles 1, 4
     • Decitabine: 15 mg/m² intravenously every 8 hours for 3 days every 6 weeks 5

Iron Overload Management

• Monitor iron status in transfusion-dependent patients
• Consider iron chelation therapy for patients with heavy transfusion requirements at risk for end-organ complications 1
• Particularly important for future candidates for allogeneic stem cell transplantation

Monitoring and Follow-up

• Regular complete blood counts to assess disease stability
• Repeat bone marrow examinations as clinically indicated
• Monitor for disease progression or transformation to AML 1

Common Pitfalls to Avoid

• Delayed risk assessment: Failure to promptly stratify patients can lead to inappropriate treatment selection
• Overlooking molecular testing: Mutations like TP53 can significantly impact prognosis and treatment response
• Inadequate transfusion support: Undertreating symptomatic cytopenias affects quality of life
• Premature treatment changes: HMAs typically require at least 4-6 cycles before assessing response
• Neglecting iron overload: Chronic transfusion therapy without monitoring iron status can lead to organ damage

The management of MDS requires a systematic approach based on risk stratification, with supportive care forming the foundation of treatment for all patients, while specific therapies are selected based on risk category and individual disease characteristics.