What is the management approach for Myelodysplastic (Myelodysplastic Syndromes, MDS) syndrome?

Management of Myelodysplastic Syndromes (MDS)

The management of myelodysplastic syndromes requires risk stratification using the Revised International Prognostic Scoring System (IPSS-R), with treatment approaches tailored to lower-risk versus higher-risk disease, where lower-risk patients should receive erythropoiesis-stimulating agents or lenalidomide (for del(5q)), and higher-risk patients should receive hypomethylating agents like azacitidine or decitabine, with allogeneic stem cell transplantation considered for eligible candidates. 1, 2

Diagnostic Approach

Initial Evaluation

• Complete blood count with differential, reticulocyte count, and examination of peripheral blood smear 1
• Bone marrow aspiration with iron stain and biopsy (mandatory) 1
• Cytogenetic analysis (mandatory) 1
• Serum erythropoietin level (prior to RBC transfusion) 1
• Biochemical parameters: iron studies, folate, vitamin B12, ferritin, LDH, bilirubin, haptoglobin 1
• Viral studies: HIV, hepatitis B/C (in transfusion-dependent patients) 1

Advanced Diagnostic Tools

• Flow cytometry immunophenotyping (recommended) 1
• FISH analysis for targeted chromosomal abnormalities when standard cytogenetics fails 1
• Mutation analysis of candidate genes (suggested) 1
• SNP array for high-resolution detection of chromosomal defects 1

Risk Stratification

• IPSS-R is the most widely accepted system for risk stratification 1, 2, 3
• Risk factors include:
  • Cytopenia severity
  • Bone marrow blast percentage
  • Cytogenetic abnormalities 1, 2
• Molecular genetic testing for mutations (e.g., TP53, RUNX1, SF3B1) provides additional prognostic information 1, 3

Treatment Approach Based on Risk

Lower-Risk MDS (IPSS-R: Very Low, Low, Intermediate)

• Primary goal: Reduce transfusion dependency, improve cytopenias, and quality of life 2, 4
• For symptomatic anemia:
  • Erythropoiesis-stimulating agents (ESAs) - first-line therapy 2, 5
  • Lenalidomide for patients with del(5q) 1, 5
  • Luspatercept for ring sideroblast subtypes (MDS-RS) after ESA failure 4, 3
• For thrombocytopenia:
  • Thrombopoiesis-stimulating agents may be considered 6
• For patients not responding to above therapies:
  • Hypomethylating agents (azacitidine or decitabine) 1, 6
  • Immunosuppressive therapy in selected patients (younger age, HLA-DR15 positivity) 6, 5

Higher-Risk MDS (IPSS-R: High, Very High)

• Primary goal: Prolong survival and delay transformation to AML 2, 4
• Hypomethylating agents:
  • Azacitidine 75 mg/m² daily for 7 days (category 1 recommendation) 1, 7
  • Decitabine as an alternative 1
  • Continue for at least 6 cycles of azacitidine or 4 cycles of decitabine to assess response 1
• Allogeneic hematopoietic stem cell transplantation (HSCT):
  • Only potentially curative option 6, 2
  • Should be considered early for eligible patients 2, 3
  • Hypomethylating agents can be used as a bridge to transplant 6
• For patients ineligible for HSCT:
  • Continue hypomethylating agents until disease progression if tolerated 1, 6

Supportive Care (All Risk Groups)

• Red blood cell transfusions for symptomatic anemia 6
• Platelet transfusions for severe thrombocytopenia or bleeding 6
• Iron chelation therapy for transfusion-dependent patients 5
• Antimicrobial prophylaxis for neutropenic patients as needed 6

Treatment Monitoring

• Regular assessment of blood counts 1
• Repeat bone marrow examination to assess response to therapy 1
• Monitor for treatment-related toxicities, especially with hypomethylating agents 7

Special Considerations

• Elderly patients (≥75 years) with good performance status can still benefit from azacitidine treatment 1
• Patients with TP53 mutations have particularly poor outcomes and may require more aggressive approaches 1, 3
• For patients with disease progression after hypomethylating agent failure, clinical trials should be considered 4, 3