Most Likely Diagnosis: Acute Lymphoblastic Leukemia (ALL)
The most likely diagnosis in a 6-month-old infant presenting with pancytopenia and organomegaly is Acute Lymphoblastic Leukemia (ALL), making option C the correct answer. Chronic myeloid leukemia is exceedingly rare in infants and typically presents with marked leukocytosis rather than pancytopenia 1. Option D (Acute non-lymphoblastic) is simply an older terminology for AML, making it equivalent to option A.
Age-Specific Epidemiology
- ALL is the most common leukemia in children, representing the majority of pediatric acute leukemias 2, 3
- Infants under 2 years with AML have distinct biology with MLL rearrangements occurring in ≥50% of cases, which is nearly exclusive to young children 1, 4
- While AML in infants commonly presents with organomegaly and pancytopenia 1, ALL remains statistically more common overall in the pediatric population 2
Clinical Presentation Supporting ALL
The combination of pancytopenia and organomegaly is characteristic of ALL:
- Organomegaly (hepatomegaly and/or splenomegaly) is found in approximately 20% of ALL patients on physical examination 2
- Lymphadenopathy frequently accompanies organomegaly in ALL 2
- Pancytopenia results from bone marrow infiltration by lymphoblasts, causing suppression of normal hematopoiesis 5, 6
Diagnostic Approach Required
Immediate bone marrow aspiration and biopsy are mandatory to establish the definitive diagnosis 2:
- Morphologic examination with Wright-Giemsa staining to identify lymphoblasts 2
- Immunophenotyping by flow cytometry is essential to distinguish ALL from AML, as misdiagnosis occurs in approximately 10% of cases without it 2
- Minimum flow cytometry panel should include CD19 plus CD22 or cytoplasmic CD79a for B-ALL, and CD7 with cytoplasmic CD3 for T-ALL 2
- Myeloperoxidase testing to exclude AML 2
Critical Diagnostic Pitfall
Special care must be taken in infants with low leukocyte counts, as immature atypical lymphocytes can mimic lymphoblasts 2. While infants with ALL usually present with high leukocyte counts, delaying treatment until bone marrow examination is completed may be preferable in those with low presenting counts 2.
Cytogenetic Considerations for Infants
If ALL is confirmed, cytogenetic analysis is critical for risk stratification 2:
- MLL (KMT2A) gene rearrangements should be tested, as they occur frequently in infant ALL 2
- Other prognostic markers include BCR-ABL1, ETV6-RUNX1, hyperdiploidy, and hypodiploidy 2