How do you manage iron levels in pediatric patients with acute myeloid leukemia (AML) who are at risk of iron overload due to frequent blood transfusions?

Management of Iron Overload in Pediatric AML Patients

Pediatric AML patients requiring frequent transfusions should begin iron chelation therapy when serum ferritin reaches 1,000 ng/mL or after receiving approximately 10-20 red blood cell transfusions (>100 mL/kg total volume), whichever comes first, and chelation should continue throughout the duration of transfusion therapy. 1, 2

Monitoring Strategy

Initial and Ongoing Assessment

• Measure serum ferritin at diagnosis to establish baseline, as 41% of pediatric leukemia patients present with ferritin >500 ng/mL and 14% with >1,000 ng/mL due to leukemic growth itself 3
• Monitor serum ferritin every 3 months in all transfusion-dependent patients to track iron accumulation 1
• Track total transfusion volume as volumes >100 mL/kg (approximately 10 transfusions) are the most important determinant of transfusional iron overload 2

Advanced Imaging When Indicated

• Obtain cardiac and hepatic T2 MRI* when ferritin exceeds 1,000 ng/mL or after 70-80 RBC units to directly assess organ iron deposition 1, 4
• Cardiac iron overload (T2* <20 ms) typically develops after >100 units of transfusion and is associated with decreased left ventricular ejection fraction 1, 5
• Hepatic iron accumulation occurs earlier, after approximately 24 units 5

Chelation Therapy Initiation Criteria

Primary Indications (All Must Be Met)

• Serum ferritin ≥1,000 ng/mL on two consecutive measurements 1
• Transfusion requirement ≥2 units/month sustained for >1 year, or cumulative volume >100 mL/kg 1, 2
• Life expectancy ≥1 year based on disease prognosis 1

Special Circumstances Requiring Earlier Chelation

• Stem cell transplant candidates should receive aggressive early chelation even with moderate iron overload, as ferritin >1,000 ng/mL at transplant is associated with higher mortality, increased treatment-related mortality, and risk of veno-occlusive disease 1, 5, 6
• Cardiac T2 <20 ms* on MRI warrants immediate chelation regardless of ferritin level 1

Chelation Agent Selection and Dosing

Deferasirox (Oral Agent - Preferred)

• Starting dose: 14-20 mg/kg/day (deferasirox tablets) for transfusional iron overload 7
• Advantages: Oral administration improves compliance compared to parenteral deferoxamine 1
• Monitor closely: Renal function (eGFR), hepatic function, and serum ferritin monthly 7

Critical Dosing Adjustments

• Reduce dose by 50% if eGFR 40-60 mL/min/1.73 m² 7
• Contraindicated if eGFR <40 mL/min/1.73 m² or platelet count <50 × 10⁹/L 7
• Interrupt therapy during acute illnesses causing volume depletion (vomiting, diarrhea, fever) as pediatric patients are at increased risk for renal toxicity 7

Transfusion Management During Chelation

Transfusion Thresholds

• Maintain hemoglobin ≥8 g/dL as minimum threshold 1
• Target hemoglobin 9-10 g/dL in patients with cardiac comorbidities or poor functional tolerance to optimize quality of life 1
• Elevated ferritin alone is NOT a contraindication to necessary transfusion therapy; transfusion decisions should be based on hemoglobin level, symptoms, and clinical status 5

Key Principle

• A single RBC unit contains only 200-250 mg of iron and will not acutely worsen iron overload in a clinically significant manner; organ damage requires approximately 420 grams of excess iron 5
• Continue necessary transfusions while maintaining concurrent chelation therapy 5, 6

Monitoring During Chelation Therapy

Laboratory Monitoring

• Serum ferritin monthly to assess chelation efficacy and prevent overchelation 7
• Renal function (eGFR and tubular function) monthly, more frequently if risk factors present 7
• Hepatic transaminases monthly as deferasirox can cause hepatotoxicity 7
• Complete blood count to monitor for cytopenias 7

Dose Adjustments Based on Response

• Consider dose reduction if ferritin <1,000 ng/mL on two consecutive visits, especially if dose >17.5 mg/kg/day 7
• Interrupt chelation if ferritin falls <500 ng/mL and continue monthly monitoring 7
• Higher rates of renal adverse events occur in pediatric patients receiving >17.5 mg/kg/day when ferritin <1,000 ng/mL 7

Special Considerations for Pediatric AML

Disease-Specific Factors

• AML patients receive more intensive transfusion support than ALL patients and finish treatment with statistically higher ferritin levels 3
• Iron overload occurs through two mechanisms: (1) pre-chemotherapy elevation from leukemic growth itself, and (2) post-chemotherapy elevation from transfusions and chemotherapy-induced autophagia 8
• Non-transferrin-bound iron (NTBI) and labile plasma iron (LPI) appear in circulation with intensive treatment, highest after hematopoietic cell transplantation 9

Age-Related Risks

• Pediatric patients are at increased risk for renal toxicity, particularly with volume depletion or when ferritin approaches normal range while on chelation 7
• Monitor more frequently during febrile illnesses, infections, or any condition causing decreased oral intake 7
• Use minimum effective dose to maintain low iron burden and prevent overchelation complications 7

Common Pitfalls to Avoid

• Do not withhold transfusions due to elevated ferritin; this worsens anemia-related cardiac strain and quality of life 1, 5
• Do not continue chelation at 14-28 mg/kg/day when ferritin approaches normal range, as this can result in life-threatening adverse events 7
• Do not ignore volume status in febrile or acutely ill children; interrupt chelation until fluid balance normalized 7
• Do not delay chelation in transplant candidates; even moderate iron overload significantly worsens transplant outcomes 1, 5, 6
• Do not rely solely on ferritin in acute illness or active leukemia, as it is an acute phase reactant; trending values over time is more reliable 1

Duration of Therapy

• Continue chelation as long as transfusion therapy continues and iron overload remains clinically relevant 1
• Reassess need for ongoing chelation in patients no longer requiring regular transfusions 7
• Post-treatment surveillance: 24-31% of pediatric leukemia patients demonstrate iron overload at treatment completion and require monitoring for potential later chelation 2, 3