What is the most likely diagnosis for a 6-month-old baby presenting with pancytopenia and organomegaly?

Most Likely Diagnosis: Acute Lymphoblastic Leukemia (ALL)

For a 6-month-old infant presenting with pancytopenia and organomegaly, acute lymphoblastic leukemia (ALL) is the most likely diagnosis among the options provided, as it is the most common childhood leukemia and frequently presents with these features in infants.

Epidemiologic Reasoning

• ALL is the most common childhood malignancy and typically presents with pancytopenia and organomegaly 1, 2
• In pediatric populations, acute leukemias (including ALL and AML) account for approximately 21% of pancytopenia cases, making them a leading malignant cause 2
• Chronic myeloid leukemia (CML) is exceedingly rare in infants and typically presents differently with marked leukocytosis rather than pancytopenia 3

Age-Specific Considerations for This 6-Month-Old

Why AML Deserves Strong Consideration

• Infants under 2 years with AML have distinct biology: MLL rearrangements occur in ≥50% of cases in this age group, which is nearly exclusive to young children 3
• AML in infants commonly presents with organomegaly and pancytopenia, particularly when associated with life-threatening symptoms from organ infiltration 3
• Acute megakaryoblastic leukemia (AMKL), a subtype of AML, can present in young children with both organomegaly and pancytopenia, though it more commonly shows leucocytosis 4

Why ALL Remains Most Likely

• ALL is statistically more common than AML across all pediatric age groups, including infants 1, 2
• ALL frequently presents with pancytopenia and organomegaly as classic features 1
• The presentation of pancytopenia with organomegaly is characteristic of ALL invading bone marrow and extramedullary sites 5, 6

Critical Diagnostic Pitfalls to Avoid

Do not assume pancytopenia rules out leukemia—some ALL cases initially present with severe pancytopenia and hypoplastic bone marrow that can mimic aplastic anemia, with malignant blasts becoming apparent only later 5, 6

Initial bone marrow examination may be misleading: In rare cases, the first bone marrow aspirate may show hypoplasia or myelodysplasia without obvious blasts, followed weeks to months later by overt leukemia 6

Peripheral blood smear is essential: Look specifically for circulating blasts, which when present confirm acute leukemia, though their absence does not exclude the diagnosis 7

Definitive Diagnostic Approach

1. Obtain complete blood count with differential and peripheral smear to identify blasts and assess cytopenia severity 7
2. Perform bone marrow aspiration and biopsy with:
   • Morphology and cytochemistry
   • Immunophenotyping by flow cytometry to distinguish ALL from AML
   • Cytogenetic analysis to identify MLL rearrangements (common in infant AML) or other prognostic markers 3
3. Assess for Down syndrome or constitutional chromosome 21 abnormalities, as these increase AML risk 14-20 fold, particularly megakaryoblastic subtype 3, 4

Why NOT Chronic Myeloid Leukemia

• CML in children typically presents with marked leukocytosis (often >100 × 10⁹/L), massive splenomegaly, and elevated platelet counts—not pancytopenia 3
• CML accounts for only 2-3% of childhood leukemias and is exceptionally rare in infants 3
• The presentation described (pancytopenia) is incompatible with typical CML, which shows myeloid proliferation 3

Answer: C - Acute Lymphoblastic Leukemia

While AML must be strongly considered given the infant's age and the high frequency of MLL rearrangements in this population 3, ALL remains the single most common childhood leukemia and most frequently presents with the described constellation of pancytopenia and organomegaly 1, 2. The definitive distinction requires bone marrow examination with immunophenotyping and cytogenetics 3.