Can ferritin supplementation be used in patients with myelodysplastic syndrome (MDS)?

Management of Iron Status in Myelodysplastic Syndrome

Iron supplementation should NOT be used in patients with myelodysplastic syndrome (MDS), as these patients are at high risk for iron overload and require iron chelation therapy rather than supplementation. 1

Iron Overload in MDS: The Problem

MDS patients frequently develop iron overload due to:

• Ineffective erythropoiesis causing increased iron absorption
• Regular red blood cell transfusions
• Underlying disease pathophysiology

Iron overload in MDS is associated with:

• Decreased overall survival 2
• Shorter leukemia-free survival 2
• Organ damage, particularly cardiac and hepatic dysfunction 1
• Increased risk of transplant-related mortality for those undergoing allogeneic stem cell transplantation 1

Monitoring Iron Status in MDS

Iron status should be assessed:

• At diagnosis of MDS 1
• Every 3 months in transfusion-dependent patients 1
• Before allogeneic stem cell transplantation 1

Key monitoring parameters:

• Serum ferritin (practical but affected by inflammation)
• Transferrin saturation
• Number of RBC transfusions received
• Organ function (cardiac, hepatic)

Advanced monitoring when available:

• MRI T2* for cardiac and liver iron content
• Liver biopsy (when clinically indicated)

When to Initiate Iron Chelation (not supplementation)

Iron chelation therapy should be initiated when:

• Serum ferritin reaches 1,000 ng/mL 1
• Patient has received ≥20 RBC units 1
• Patient has transfusion requirement of ≥2 units/month for >1 year 1
• Patient is a candidate for allogeneic stem cell transplantation 1
• Evidence of organ dysfunction from iron overload exists 1

Iron Chelation Options for MDS

1. Deferasirox (oral)

   • First-line option for most patients 1
   • Contraindicated in renal failure 1
   • Effectively reduces liver iron concentration and serum ferritin 3, 4
   • May improve hematologic parameters and liver function 4

2. Deferoxamine (parenteral)

   • Alternative when oral therapy is not tolerated 1
   • Requires subcutaneous administration

3. Deferiprone (oral)

   • Limited use in MDS due to risk of agranulocytosis 1
   • May be considered at 75 mg/kg/day when other options aren't available 5
   • Not approved for MDS in most countries 1

Special Considerations

Hematologic Improvement with Iron Management

Some studies suggest potential hematologic benefits from proper iron management:

• Improved hemoglobin levels with chelation 4
• Increased platelet counts 4
• Reduced transfusion requirements 4

Erythropoiesis-Stimulating Agents (ESAs) and Iron

When using ESAs for anemia in MDS:

• Monitor iron parameters closely 6
• Consider that functional iron deficiency may occur despite high ferritin 6
• Oral sucrosomial iron may improve ESA response in specific cases of functional iron deficiency 7

Common Pitfalls to Avoid

1. Misinterpreting high ferritin

   • High ferritin in MDS often reflects inflammation and disease activity, not just iron stores 6
   • Functional iron deficiency can occur despite elevated ferritin 6

2. Inappropriate iron supplementation

   • Adding iron to patients with existing iron overload worsens organ toxicity
   • Transfusion-dependent MDS patients rarely need iron supplementation

3. Inadequate monitoring

   • Failure to regularly assess iron parameters
   • Not considering organ function assessment

4. Delaying chelation therapy

   • Particularly problematic in transplant candidates
   • Can lead to irreversible organ damage

In conclusion, iron supplementation with ferritin is contraindicated in MDS patients who typically have iron overload requiring chelation therapy rather than supplementation. The focus should be on monitoring iron status and implementing appropriate chelation strategies to reduce morbidity and mortality.