How would you manage Acute Myeloid Leukemia (AML) in a 15-month-old baby with Epstein's anomaly, Supraventricular Tachycardia (SVT), and Wolff-Parkinson-White (WPW) syndrome, who has recently undergone open-heart surgery?

Management of AML in a 15-Month-Old with Severe Ebstein's Anomaly, SVT, WPW, and Recent Open-Heart Surgery

This infant requires immediate multidisciplinary coordination between pediatric oncology, cardiology, and cardiac surgery teams at a tertiary center, with AML treatment initiated urgently while managing cardiac arrhythmias medically, and consideration of intraoperative arrhythmia ablation if further cardiac surgery becomes necessary. 1

Immediate Priorities: AML Treatment Cannot Be Delayed

• AML is a medical emergency and treatment delay compromises survival—chemotherapy must begin promptly despite the cardiac complexity. 1
• Standard induction therapy for pediatric AML consists of 7-10 days of cytarabine with 3 days of anthracycline (daunorubicin preferred over idarubicin in complex cases), achieving complete remission in >85% of children. 2, 1
• For infants under 2 years, dosing should be calculated by body weight (mg/kg) rather than body surface area due to altered pharmacokinetics and organ immaturity. 2
• High-dose cytarabine dosing requires age adjustment in children under 2 years due to reduced clearance. 2

Critical Cardiac Considerations During Chemotherapy

Anthracycline Cardiotoxicity Management

• Cumulative anthracycline doses >300 mg/m² cause significant cardiac toxicity—this is particularly concerning given pre-existing severe Ebstein's anomaly and recent cardiac surgery. 1, 3
• Baseline echocardiography is mandatory before starting anthracyclines, with serial monitoring throughout treatment. 3
• Consider dose reduction or alternative regimens if cardiac function deteriorates, though this must be balanced against leukemia control. 1

Arrhythmia Management During Chemotherapy

• Beta-blockers are first-line for SVT/WPW management in this infant, with digoxin added for treatment failures—however, digoxin monotherapy should be avoided in WPW. 4
• Procainamide can be added as third-line therapy if beta-blockers and digoxin combination fails. 4
• Catheter ablation should be performed with extreme caution in Ebstein's anomaly patients due to lower success rates (75-89% acute success with 25-30% acute recurrence) compared to other populations. 2
• Percutaneous ablation carries risk of paradoxical embolus if interatrial communication with right-to-left shunt exists. 2

Optimal Timing for Arrhythmia Intervention

If the infant requires reoperation for tricuspid valve issues or worsening Ebstein's anomaly during AML treatment, intraoperative surgical ablation of accessory pathways should be performed simultaneously, as this approach is more effective (92-100% success) than catheter ablation in Ebstein's patients. 2, 5

• Combined operative arrhythmia surgery with cardiac repair is effective in 94% of cases versus 76% with catheter ablation alone in Ebstein's patients. 2
• Patients undergoing preoperative EP study with intraoperative ablation have lower risk of sudden cardiac death than those without arrhythmia intervention. 2
• Right-sided accessory pathways are present in 15-30% of Ebstein's patients and may be multiple in up to 29%. 2

Supportive Care Essentials

Tumor Lysis Syndrome Prevention

• Aggressive hydration, allopurinol or rasburicase, and continuous electrolyte monitoring are mandatory given the high risk in AML. 1, 3
• Monitor for hyperleukocytosis and signs of leukostasis—cytoreduction with hydroxycarbamide or cytarabine may be necessary. 3

Infection Prophylaxis

• Neutropenic fever protocols must be rigorously followed given the immunosuppression from both chemotherapy and recent cardiac surgery. 1

CNS-Directed Therapy

• All pediatric AML patients receive CNS prophylaxis with intrathecal chemotherapy (cytarabine or methotrexate) starting at diagnosis. 2, 1
• Cranial irradiation has been abandoned due to late toxicities and lack of superiority over high-dose cytarabine, which crosses the blood-brain barrier. 2

Response Assessment and Consolidation

• Bone marrow evaluation should occur after hematological recovery from induction (days 28-35) and before each consolidation cycle. 1, 3
• Complete remission is defined as normal bone marrow cellularity with <5% blasts and recovery of normal hematopoiesis. 1, 3
• Consolidation strategy depends on risk stratification—favorable risk patients receive high-dose cytarabine-based consolidation, while intermediate/high-risk patients should consider allogeneic stem cell transplantation. 1, 3

Critical Pitfalls to Avoid

• Do not delay AML treatment waiting for "optimal" cardiac status—the leukemia will progress rapidly and become refractory. 1
• Do not use digoxin monotherapy for WPW—it can paradoxically accelerate conduction through accessory pathways. 4
• Do not attempt catheter ablation without careful consideration of interatrial shunts and the lower success rates in Ebstein's patients. 2
• Monitor cumulative anthracycline dose meticulously given the pre-existing cardiac disease. 1, 3
• Ensure treatment occurs at a tertiary center with pediatric oncology, congenital heart disease expertise, and cardiac surgery capabilities. 2, 1

Long-Term Surveillance

• Lifelong specialized cardiac surveillance is required for recurrent tricuspid valve dysfunction, prosthetic valve degeneration, atrial and ventricular arrhythmias, and ventricular dysfunction. 2
• Oncologic follow-up includes physical examination and blood tests every 3-6 months for the first two years, with monitoring for late effects including cardiotoxicity and secondary malignancies. 1