In a patient with a six‑month history of pallor, pancytopenia and organomegaly, which type of leukemia is most likely?

Chronic Myeloid Leukemia (CML) is Most Likely

Given a six-month history of pallor, pancytopenia, and organomegaly, chronic myeloid leukemia (CML) is the most likely diagnosis (Answer B). The prolonged six-month duration with organomegaly strongly favors a chronic leukemia over acute presentations, and the specific constellation of findings points to CML rather than other leukemia types.

Key Distinguishing Features Supporting CML

Clinical Presentation Timeline

• CML characteristically presents with an insidious onset over months, with approximately 40-50% of patients being asymptomatic at diagnosis and discovered incidentally on routine blood work 1, 2.
• The six-month history of symptoms aligns with CML's chronic phase presentation, whereas acute leukemias (AML, ALL) typically present with rapid onset over days to weeks 2.

Organomegaly Pattern

• Splenomegaly is the most consistent physical finding in CML, detected in 40-50% of cases at diagnosis 1.
• Hepatomegaly occurs less commonly but is still characteristic of CML 1.
• This organomegaly pattern with prolonged symptoms is pathognomonic for CML in chronic phase 1.

Pancytopenia Context

• While CML classically presents with marked leukocytosis (often exceeding 100 × 10⁹/L), thrombocytosis, and basophilia 2, 3, 4, the question describes pancytopenia, which suggests either:
  • Early chronic phase CML with anemia (common presenting feature) 1
  • CML with bone marrow fibrosis (present in 30% of cases) causing relative cytopenias 1
  • Possible progression toward accelerated phase 1

Why Not Acute Leukemias?

Against Acute Myeloid Leukemia (AML)

• AML typically presents acutely with symptomatic disease including fatigue, bleeding, and fever, not a six-month indolent course 2.
• AML shows cytopenias with circulating blasts and lacks orderly myeloid maturation 2.
• The prolonged timeline with organomegaly is inconsistent with untreated AML 2.

Against Acute Lymphoblastic Leukemia (ALL)

• ALL presents with rapid onset of symptoms, not a six-month chronic course.
• ALL does not characteristically present with significant organomegaly as a primary feature.

Note on Answer Choice D

• "Acute non-lymphoblastic" is an outdated term synonymous with AML, making options A and D essentially identical 2.

Diagnostic Confirmation Required

The diagnosis must be confirmed by demonstrating the Philadelphia chromosome t(9;22)(q34;q11) through cytogenetics and BCR-ABL1 fusion gene by RT-PCR 1, 5, 3, 4.

• Conventional cytogenetics identifies the Philadelphia chromosome in 90-95% of CML cases 5.
• BCR-ABL1 testing is mandatory and must be positive to confirm CML diagnosis 2, 5.

Clinical Pitfall to Avoid

The presence of pancytopenia should not mislead you away from CML diagnosis. While CML classically presents with leukocytosis, anemia is a common presenting symptom resulting from splenomegaly and bone marrow changes 1. Additionally, moderate to marked reticulin fibrosis occurs in 30% of CML cases at diagnosis, which can contribute to cytopenias 1. The key discriminating features remain the six-month chronic timeline and organomegaly, which are characteristic of CML chronic phase rather than acute leukemias 1, 2.