At what ferritin level should chelation therapy be initiated in patients receiving repeated blood transfusions?

Initiation of Chelation Therapy in Patients Receiving Repeated Blood Transfusions

Chelation therapy should be initiated when serum ferritin levels reach 1,000 ng/mL in transfusion-dependent patients, particularly when their transfusion need is 2 units/month or more for greater than one year. 1

Patient Selection Criteria for Chelation Therapy

Iron chelation therapy should be considered in patients who meet the following criteria:

• Serum ferritin levels ≥1,000 ng/mL
• Transfusion dependency (requiring ≥2 units/month for >1 year)
• Life expectancy of at least one year
• Patients with low-risk hematological conditions (e.g., low-risk MDS, IPSS low or intermediate-1)
• Patients being considered for allogeneic stem cell transplantation
• Patients in whom organ function preservation is needed

Evidence of Iron Overload

Before initiating chelation therapy, confirm iron overload through:

• Serial serum ferritin measurements (at least 2-3 readings >1,000 ng/mL)
• Transfusion history (≥20 units of packed red blood cells or equivalent)
• Consider liver MRI to quantify hepatic iron concentration if ferritin remains >1,000 ng/mL 2

Monitoring Iron Overload

• Assess iron stores at diagnosis of the underlying condition
• For transfusion-dependent patients, monitor serum ferritin every 3 months (monthly if possible) 1
• Monitor organ function periodically:
  • Cardiac function assessment
  • Liver function tests every 3 months
  • Complete blood count before each chelation treatment
  • Renal function tests

Chelation Agent Selection

For patients with confirmed iron overload (serum ferritin >1,000 ng/mL):

1. Deferasirox (oral agent):

   • Initial dose: 14 mg/kg/day for patients with eGFR >60 ml/min/1.73m² 3
   • Adjust dose every 3-6 months based on ferritin trends
   • Maximum dose: 28 mg/kg/day

2. Deferoxamine (parenteral):

   • Consider for patients with cardiac complications or those who cannot tolerate oral chelators
   • Typically administered as subcutaneous infusion

3. Combination therapy:

   • May be considered for patients with severe iron overload not responding to monotherapy

Duration of Chelation Therapy

• Continue chelation as long as the patient requires regular transfusions 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

Special Considerations

Stem Cell Transplant Candidates

• Iron chelation prior to SCT decreases risk for procedure-related hepatic complications
• Higher mortality is seen with ferritin levels >1,000 ng/mL at SCT 1

Post-Transplant Management

• Avoid iron chelation during ongoing immunosuppressive therapy
• Consider phlebotomy for iron unloading in patients with favorable prognosis >1 year after SCT and adequate, stable hemoglobin

Pitfalls and Caveats

• Overtreatment: Reducing ferritin below 50 μg/L can increase dietary iron absorption and cause symptomatic iron deficiency 2
• Undertreatment: Continued organ damage due to inadequate iron removal
• Misinterpretation: Elevated ferritin can be due to inflammation, not just iron overload
• Contraindications: Avoid chelation in patients with severe hepatic impairment (Child-Pugh C) 3
• Monitoring: Regular assessment of renal function is essential, especially with deferasirox

The 1,000 ng/mL ferritin threshold is supported by multiple studies showing increased mortality and organ dysfunction when this level is exceeded in transfusion-dependent patients 4. This threshold has been consistently recommended in clinical guidelines for initiating chelation therapy to prevent iron-related organ damage and improve survival.