What are the treatment options for myelodysplastic (myelodysplastic syndromes) anemia?

Treatment Options for Myelodysplastic Syndrome (MDS) Anemia

Treatment of MDS anemia is stratified by disease risk (IPSS/IPSS-R score) and specific cytogenetic features, with lower-risk patients prioritizing quality of life through correction of cytopenias, while higher-risk patients require disease-modifying therapy to alter natural history and improve survival. 1

Risk Stratification Framework

Treatment decisions depend critically on prognostic risk category:

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

The primary therapeutic goal differs fundamentally between these groups—hematologic improvement and quality of life for lower-risk disease versus altering disease natural history for higher-risk disease 1.

Lower-Risk MDS: Treatment Algorithm for Anemia

First-Line Treatment Selection

For patients WITHOUT del(5q):

• Erythropoiesis-stimulating agents (ESAs) are first-line therapy 1
• Use recombinant EPO (30,000-80,000 units weekly) or darbepoetin (150-300 μg weekly) 1
• Achieve ~40-60% erythroid response rates when baseline EPO <200-500 U/L and transfusion requirement is low/absent 1
• Response occurs within 8-12 weeks; median duration ~2 years 1
• Adding G-CSF improves efficacy 1
• ESAs provide survival benefit independent of AML progression risk 1

For patients WITH del(5q):

• Lenalidomide is first-line therapy 1
• Dose: 10 mg daily for 3 weeks every 4 weeks 1
• Achieves 60-65% RBC transfusion independence with median duration 2-2.5 years 1
• Produces cytogenetic response in 50-75% (30-45% complete) 1
• Critical caveat: Grade 3-4 neutropenia/thrombocytopenia occurs in ~60% during first weeks—requires close monitoring and potential dose reduction 1
• TP53 mutations (~20% of del(5q) cases) predict resistance and higher AML risk—these patients need intensified surveillance or alternative approaches 1

Second-Line Options After ESA/Lenalidomide Failure

Treatment after first-line failure remains challenging, with most patients eventually requiring chronic transfusions 1:

• Luspatercept: Particularly effective in SF3B1-mutated or ring sideroblast-positive MDS 1
• Hypomethylating agents (azacitidine, decitabine): Can produce erythroid responses 1
• Immunosuppressive therapy (anti-thymocyte globulin): 30-40% response rate in selected patients 1

Higher-Risk MDS: Disease-Modifying Therapy

The treatment goal shifts to altering disease natural history and improving survival 1:

Definitive Treatment Options

• Allogeneic stem cell transplantation: Only curative option for eligible patients 1

  • Patients <55 years without comorbidities should receive myeloablative conditioning 1
  • Matched sibling or unrelated donors preferred 1
  • Iron chelation recommended before transplant to reduce treatment-related mortality 1

• Hypomethylating agents (azacitidine, decitabine): For non-transplant candidates 1, 2

  • Decitabine: 15 mg/m² IV over 3 hours every 8 hours for 3 days, repeat every 6 weeks OR 20 mg/m² IV over 1 hour daily for 5 days, repeat every 4 weeks 2
  • Indicated for all IPSS intermediate-1, intermediate-2, and high-risk groups 2

• AML-like chemotherapy: For younger patients with good performance status 1

Supportive Care: Universal Foundation

All patients require comprehensive supportive care regardless of risk category 1:

Transfusion Management

• RBC transfusions: Administer when hemoglobin <8-10 g/dL depending on symptoms and comorbidities 1
• Use leukocyte-reduced products 1
• Irradiate directed-donor products and all products for potential transplant candidates 1
• CMV-negative products for CMV-negative recipients 1
• Transfuse sufficient units to raise hemoglobin >10 g/dL to limit chronic anemia effects on quality of life 1

Iron Overload Management

Critical consideration: Transfusion dependency worsens survival, particularly in lower-risk MDS 1:

• Monitor serum ferritin and transfusion burden 1
• Iron overload (ferritin >1,000 ng/mL) increases mortality by 30% for every 500 ng/mL increase 1
• Consider chelation therapy to maintain ferritin <1,000 mcg/L in patients with chronic transfusion needs and reasonable life expectancy 1
• Pre-transplant iron chelation reduces treatment-related mortality 1

Management of Other Cytopenias

• Neutropenia with infection: G-CSF or GM-CSF for recurrent/resistant bacterial infections 1
• Thrombocytopenia: Platelet transfusions for severe thrombocytopenia or bleeding; aminocaproic acid for refractory bleeding 1
• TPO receptor agonists (romiplostim, eltrombopag) under investigation for thrombocytopenia 1

Key Clinical Pitfalls

Avoid delayed treatment initiation in non-transfusion-dependent patients with symptomatic anemia—this leads to unnecessary morbidity and decreased quality of life 1. Transfusion dependency itself is a negative prognostic factor independent of iron overload 1, making active treatment preferable to chronic transfusions when feasible 1.