Initiation of Iron Chelation Therapy in Pediatric Patients
Primary Recommendation
Iron chelation therapy in pediatric patients should be initiated when serum ferritin reaches ≥1,000 ng/mL OR when the transfusion burden is ≥2 units per month sustained for more than one year, provided the child has a life expectancy of at least one year. 1
Key Initiation Criteria
Ferritin-Based Threshold
- Start chelation when serum ferritin reaches 1,000 ng/mL, particularly in children with chronic transfusion-dependent conditions 1
- This threshold is associated with significantly worsened survival when exceeded 1
Transfusion Burden Criteria
- Initiate therapy when transfusion requirement is ≥2 units/month for >1 year 1
- Cardiac abnormalities develop after >100 units of transfusions 1
- Liver iron accumulation occurs after >24 units of transfusions 1
Age-Specific Considerations
- Safety and effectiveness are established for children ≥3 years of age 2
- Children <3 years should NOT receive chelation unless significant iron mobilization (≥1 mg iron/day) can be demonstrated 2
- Iron mobilization is relatively poor in children <3 years with minimal iron overload 2
- Evidence for children ≥2 years with transfusional iron overload is widely available 3
Special Clinical Scenarios Requiring Early Initiation
Pre-Transplant Patients
- Candidates for allogeneic stem cell transplant should be chelated early, even with moderate iron overload 1
- Ferritin >1,000 ng/mL at transplant is associated with higher mortality 1
- Iron chelation prior to transplant decreases procedure-related hepatic complications 1
Organ Preservation
- Initiate chelation when there is need to preserve organ function, regardless of ferritin level 1
- This applies even in patients with life expectancy <1 year if they already show signs of iron-related organ complications 1
- Cardiac T2* <20 milliseconds by MRI indicates significant heart iron overload and warrants chelation 1
Monitoring Requirements Before and During Therapy
Baseline Assessment
- Assess body iron stores at diagnosis of the underlying condition 1
- Establish transfusion tracking system to monitor cumulative burden 1
Ongoing Monitoring
- Check serum ferritin every 3 months (monthly if possible) in transfusion-dependent patients 1
- Monitor organ function periodically 1
- Assess growth parameters (weight and height) every 3 months in pediatric patients, as high doses with low ferritin levels can suppress growth 2
Contraindications and Precautions
Absolute Contraindications
- Severe renal disease (contraindication for deferoxamine) 2
- Age <3 years without demonstrable iron mobilization 2
Important Safety Considerations
- Start at low end of dosing range in patients with renal or hepatic impairment 2
- Monitor for increases in serum creatinine, acute renal failure, and renal tubular disorders 2
- High doses combined with low ferritin levels are associated with growth suppression 2
- Avoid post-transplant chelation during ongoing immunosuppressive therapy due to overlapping renal toxicity 1
Patient Selection Algorithm
Initiate chelation if ANY of the following:
- Serum ferritin ≥1,000 ng/mL with ongoing transfusions 1
- Transfusion burden ≥2 units/month for >1 year 1
- Candidate for allogeneic transplant with elevated iron stores 1
- Evidence of organ dysfunction from iron overload (cardiac T2* <20 ms, liver dysfunction) 1
- Life expectancy ≥1 year (exception: existing organ damage requiring preservation) 1
Do NOT initiate if:
- Age <3 years without demonstrable iron mobilization 2
- Severe renal disease 2
- Life expectancy <1 year without existing organ damage 1
Available Chelation Options
Three iron chelators are available with established safety profiles in pediatric populations ≥2-3 years 3, 4, 5: