What is the recommended treatment approach for iron chelating therapy in patients with iron overload conditions?

Iron Chelation Therapy for Iron Overload Conditions

Iron chelation therapy should be initiated when serum ferritin levels reach 1,000 ng/mL or when transfusion needs are ≥2 units/month for more than one year, with the choice of chelating agent (deferoxamine, deferiprone, or deferasirox) determined by the treating physician based on patient characteristics and clinical context. 1, 2

Patient Selection for Iron Chelation Therapy

Iron chelation therapy is indicated for patients with:

• Serum ferritin levels >1,000 ng/mL 1, 2
• Transfusion dependency requiring ≥2 units/month for >1 year 1
• Low-risk myelodysplastic syndromes (MDS) 1
  • IPSS low or intermediate-1
  • WHO classification of RA, RARS, or 5q-
• Life expectancy of at least one year 1
• Patients without comorbidities that would limit prognosis 1
• Candidates for allogeneic stem cell transplantation 1
• Idiopathic myelofibrosis with favorable or intermediate prognostic score 1

Iron Chelating Agents and Administration

Three FDA-approved iron chelators are available:

1. Deferoxamine (Desferal):

   • Administration: Subcutaneous, intravenous, or intramuscular 3
   • Dosing:
     • Subcutaneous: 40-50 mg/kg/day via slow infusion over 8-12 hours, 5-7 times/week 3
     • Intravenous: 40-50 mg/kg/day over 8-12 hours at a rate up to 15 mg/kg/hour, 5-7 days/week 3
     • Intramuscular: 500-1,000 mg/day 3
   • Maximum dose: 60 mg/kg/day for adults, 40 mg/kg/day for pediatric patients 3

2. Deferiprone (Ferriprox):

   • Administration: Oral, three times daily 4
   • Advantages: May be more effective for cardiac iron chelation 4
   • Side effects: Gastrointestinal symptoms, liver dysfunction, joint pain, neutropenia, and agranulocytosis 4
   • Monitoring: Weekly assessment of white blood cell counts due to risk of agranulocytosis 4

3. Deferasirox (Exjade):

   • Administration: Once-daily oral administration 5
   • Long half-life (16-18 hours) providing 24-hour iron chelation coverage 4
   • Efficacy established in various conditions including beta-thalassemia, MDS, sickle cell disease, and aplastic anemia 5

Monitoring During Iron Chelation Therapy

• Serum ferritin levels: Every 3 months, monthly if possible 1, 2
• Complete iron studies (serum ferritin, transferrin saturation) 2
• Liver function tests 2
• Target ferritin level: 50-100 μg/L 2
• For patients on deferoxamine: Auditory and visual testing 2
• For patients on deferasirox: Renal function monitoring 2
• Cardiac function assessment 2

Special Considerations

Post-Stem Cell Transplantation

• Iron chelation therapy prior to SCT decreases risk for procedure-related hepatic complications 1
• Higher mortality is seen with ferritin levels >1,000 ng/mL at SCT 1
• Avoid iron chelation therapy post-transplant during ongoing immunosuppressive therapy due to risk of overlapping renal toxicity 1
• Phlebotomy is the preferred method for iron unloading in patients with favorable prognosis >1 year after SCT and adequate, stable hemoglobin 1

Vitamin C Supplementation

• Patients with iron overload usually become vitamin C deficient 3
• As adjuvant to iron chelation therapy, vitamin C may be given in doses up to 200 mg for adults in divided doses 3
• Start vitamin C supplementation after an initial month of regular treatment with deferoxamine 3
• Limit vitamin C supplementation to <500 mg/day to avoid accelerating iron mobilization and increasing toxicity 2

Duration of Therapy

• Chelation therapy should continue as long as the patient has a need for transfusion therapy and iron overload remains clinically relevant 1
• Therapy can be withheld when ferritin level declines to <1,000 ng/mL and no additional transfusions are needed 1
• Therapy may be discontinued if it is no longer in the best interest of the patient 1

Common Pitfalls and Caveats

• Avoid overtreatment leading to iron deficiency (ferritin <50 μg/L) 2
• Don't misinterpret elevated ferritin as iron overload when it could be due to inflammation 2
• Evaluate for other causes of elevated iron (hereditary hemochromatosis, transfusional iron overload) 2
• Established cirrhosis will not reverse with iron removal, though portal hypertension may improve 2
• Patients with iron overload should avoid iron-fortified foods, limit red meat consumption, and avoid raw shellfish due to increased risk of Vibrio vulnificus infection 2