What is the treatment for iron overload due to serial blood transfusions?

Treatment of Iron Overload Due to Serial Blood Transfusions

Iron chelation therapy should be initiated in transfusion-dependent patients who have received or are anticipated to receive more than 20 units of red blood cells, have serum ferritin levels >1,000 ng/mL, and have a life expectancy of at least one year. 1

Monitoring for Iron Overload

Before initiating treatment, iron overload should be assessed and monitored using:

• Serum ferritin levels: Primary monitoring parameter, measured every 3 months in transfusion-dependent patients 1
• Transferrin saturation: Supplementary measurement, though less reliable due to daily variability and influence of inflammation 1
• Advanced imaging techniques (when available):
  • MRI T2* for liver and cardiac iron content
  • SQUID (Superconducting Quantum Interference Device) for liver iron quantification 1

Iron Chelation Therapy Options

Three main chelating agents are available:

1. Deferasirox (Exjade):

   • Oral, once-daily administration (20-30 mg/kg/day)
   • First-line option due to convenience of oral administration 1, 2
   • Effectively reduces serum ferritin and liver iron concentration 3
   • Monitoring requirements: Renal function (serum creatinine), liver function tests, and complete blood counts before initiation and regularly thereafter 2
   • Black box warning for renal failure, hepatic failure, and gastrointestinal hemorrhage 1

2. Deferoxamine (Desferal):

   • Administered subcutaneously (40-60 mg/kg, 8-12 hours, 5 days per week)
   • Long-established efficacy but limited by parenteral administration 4
   • Consider for patients who cannot tolerate deferasirox

3. Deferiprone:

   • Oral administration (50-120 mg/kg/day)
   • Not available in the United States
   • Used in Europe when deferoxamine is inadequate or contraindicated 1

Patient Selection for Chelation Therapy

Iron chelation therapy is most beneficial for:

• Patients with low-risk MDS (IPSS low or intermediate-1, WHO RA, RARS, and 5q-) 1
• Transfusion-dependent patients requiring ≥2 units/month for >1 year 1
• Patients with serum ferritin levels >1,000 ng/mL 1
• Patients with life expectancy of at least one year 1
• Patients without comorbidities that would limit prognosis 1
• Candidates for allogeneic stem cell transplantation 1

Duration of Therapy

Chelation therapy should be continued as long as:

• The patient remains transfusion-dependent
• Iron overload remains clinically relevant 1

Therapy can be withheld when:

• Ferritin levels decline to <1,000 ng/mL and no additional transfusions are needed
• It is no longer in the best interest of the patient 1

Special Considerations

1. Allogeneic stem cell transplant candidates: Iron chelation therapy prior to transplant decreases the risk of procedure-related hepatic complications and mortality 1

2. Post-transplant iron removal:

   • Phlebotomy is preferred for patients with stable hemoglobin >1 year after transplant
   • Avoid chelation during immunosuppressive therapy due to risk of overlapping renal toxicity 1

3. Monitoring for adverse effects:

   • With deferasirox: Monitor renal function, liver function, and complete blood counts 2
   • Watch for gastrointestinal disturbances, skin rash, and changes in renal parameters 3

4. Potential hematological improvement: Some evidence suggests iron chelation may improve hematopoiesis in certain patients 5, though this requires further investigation

By implementing appropriate iron chelation therapy, the goal is to decrease serum ferritin levels to <1,000 ng/mL, prevent iron-related organ dysfunction, and ultimately improve survival and quality of life in transfusion-dependent patients.