What is the treatment approach for Acute Myeloid Leukemia (AML) in a newborn?

Treatment of AML in Newborns

For true de novo AML in newborns, treat with intensive multi-agent chemotherapy using anthracyclines and cytarabine with age-adjusted dosing (mg/kg rather than body surface area), but first rule out Down syndrome-associated transient leukemia which may require only observation or low-dose cytarabine for life-threatening symptoms. 1, 2

Critical Initial Distinction

Down Syndrome Screening

• Immediately assess for Down syndrome or DS mosaicism, as approximately 5% of newborns with DS present with transient leukemia (transient abnormal myelopoiesis) that spontaneously resolves in 4-10 weeks 1
• Test for GATA1 mutations in exon 2, which characterize both transient leukemia and myeloid leukemia of Down syndrome (ML-DS) 1
• Most newborns with DS-associated transient leukemia experience spontaneous remission without treatment 1

When to Intervene in DS-Associated Disease

Intervene only if life-threatening symptoms develop: 1

• Hyperleukocytosis causing organ dysfunction
• Hydrops fetalis (most severe complication)
• Life-threatening pleural effusions or ascites
• Fatal liver cirrhosis with conjugated bilirubin >250 μmol/L in first weeks of life

Treatment for symptomatic DS transient leukemia: 1

• Exchange transfusion and/or
• Low-dose cytarabine chemotherapy: 1-1.5 mg/kg × 5-7 days

True De Novo AML Management in Newborns

Diagnostic Workup

Complete the following before initiating therapy: 1

• Bone marrow aspirate with morphology, cytochemistry, immunophenotyping
• Karyotyping, FISH, and molecular genetics
• Defer lumbar puncture if severe thrombocytopenia or coagulopathy present until bleeding risk resolves 1
• Rule out congenital infections before confirming leukemia diagnosis 2

Biological Characteristics in Neonates

Newborns (<2 years) have distinct high-risk features: 1

• MLL rearrangements occur in ≥50% of cases
• Rare aberrations nearly exclusive to this age: t(7;12), t(1;22)/RBM15-MKL1
• Core-binding factor AML and t(15;17) are rarely seen
• Increased organ immaturity (lung, liver, brain) heightens toxicity susceptibility

Chemotherapy Approach

Dosing Adjustments: 1

• Calculate all chemotherapy doses by body weight (mg/kg) rather than body surface area
• Children <2 years have reduced cytarabine clearance, requiring age-adjusted HiDAC dosing
• Standard regimen: anthracyclines plus cytarabine (similar to older children but dose-adjusted)

Treatment Intensity: 1, 2

• Management principles are not fundamentally different from older children
• Intensive multi-agent chemotherapy is standard
• Age-related dose adjustments are mandatory to account for pharmacokinetic/pharmacodynamic differences

Prognosis Considerations

• Neonatal AML has better prognosis than neonatal ALL 2
• High mortality rates remain due to treatment-related toxicity and organ immaturity 2
• MLL rearrangements confer high-risk biology 1

Supportive Care Priorities

Infection Prophylaxis

• Consider fluoroquinolone prophylaxis for expected prolonged neutropenia (ANC <100/μL for >7 days), though not licensed in children 1
• Do not use prophylactic G-CSF routinely - it decreases neutropenia duration but doesn't reduce infection-related mortality 1

Critical Monitoring

• Aggressive hydration for tumor lysis syndrome prevention 3
• Rasburicase for hyperuricemia management 3
• Cardiac monitoring given anthracycline cardiotoxicity risk (cumulative doses >300 mg/m² associated with significant toxicity) 4

Common Pitfalls

• Failing to screen for Down syndrome before initiating intensive chemotherapy - this is the most critical error as many DS newborns need only observation 1
• Using body surface area dosing instead of weight-based dosing in infants 1
• Performing lumbar puncture in presence of coagulopathy or severe thrombocytopenia 1
• Misdiagnosing congenital infections as leukemia 2
• Routine use of G-CSF (not beneficial and may increase relapse risk in certain genetic subtypes) 1