Initial Treatment Approach for Myelodysplastic Syndrome
The initial treatment of MDS is determined by risk stratification using IPSS-R, which divides patients into lower-risk and higher-risk groups requiring fundamentally different therapeutic strategies. 1
Risk Stratification First
Before initiating any disease-directed therapy, stratify patients using the International Prognostic Scoring System-Revised (IPSS-R), which incorporates cytopenias, bone marrow blast percentage, cytogenetic abnormalities, and molecular mutations. 1 This classification determines whether the patient falls into lower-risk (better prognosis, median survival 3-10 years) or higher-risk disease (median survival <3 years). 2
Patient-specific factors including age, performance status, comorbidities, and transfusion requirements further guide treatment selection. 1
Lower-Risk MDS Treatment Algorithm
For Anemia WITHOUT del(5q):
Start with erythropoiesis-stimulating agents (ESAs) as first-line therapy at weekly doses of 30,000-80,000 units of erythropoietin or darbepoetin 150-300 μg. 1 ESAs improve anemia in 15-40% of patients for a median duration of 8-23 months. 2
For Anemia WITH del(5q):
Lenalidomide is the most effective first-line treatment, achieving 60-65% response rates with median transfusion independence lasting 2-2.5 years. 1 This represents superior efficacy compared to ESAs in this cytogenetic subgroup.
For Severe Thrombocytopenia:
Use TPO receptor agonists (romiplostim or eltrombopag) only in patients with marrow blasts <5%, as higher blast counts increase risk of progression. 1
Higher-Risk MDS Treatment Algorithm
For Patients NOT Immediately Eligible for Transplant:
Initiate azacitidine 75 mg/m² daily for 7 consecutive days every 28 days as first-line therapy. 1, 3 This hypomethylating agent is FDA-approved for all FAB subtypes of MDS and provides modest survival benefit with approximately 40% response rates. 3, 4
Administer at least 6 cycles before assessing response, as most patients only respond after several courses. 5 Decitabine represents an alternative hypomethylating agent with similar FDA approval for all MDS subtypes. 6
For Fit Patients ≤70 Years with a Donor:
Allogeneic stem cell transplantation should be proposed to all higher-risk MDS patients without major comorbidities who have a donor, as this represents the only potentially curative option. 1, 2 This should be considered at diagnosis for higher-risk patients. 2
Essential Supportive Care Measures
Red Blood Cell Transfusions:
Transfuse for symptomatic anemia at hemoglobin thresholds of at least 8 g/dL, or 9-10 g/dL in patients with cardiovascular comorbidities. 1, 5 Individualize thresholds between 8-10 g/dL based on clinical status rather than arbitrary targets. 5
Iron Chelation Therapy:
Initiate iron chelation for:
- Transplant candidates with iron overload 1
- Non-transplant candidates with major iron overload 1
- Patients with favorable prognosis who have received 20-60 RBC units or serum ferritin >1000-2500 U/L 1
Iron overload from chronic transfusions causes significant morbidity if left untreated. 7
Infection Management:
Immediately start broad-spectrum antibiotics for any fever or infection symptoms in neutropenic patients. 5 G-CSF can be added during severe infections (improves neutropenia in 60-75% of cases), but prolonged prophylactic use has not demonstrated survival benefit. 5
Critical Pitfalls to Avoid
Do not substitute oral azacitidine formulations for injectable azacitidine, as they have different indications and dosing regimens. 3
Do not discontinue hypomethylating agents prematurely—responses often require multiple cycles before becoming apparent. 5
Do not use TPO receptor agonists in patients with ≥5% bone marrow blasts due to progression risk. 1
Do not delay allogeneic transplant evaluation in fit, higher-risk patients with available donors, as this is the only curative option. 1, 2