In a 13-year-old boy with three months of high‑grade fever (105 °F), anemia (Hb 6.5 g/dL), thrombocytosis, leukocytosis (WBC 25 × 10⁹/L) and who has received two blood transfusions, what is the most likely diagnosis and appropriate treatment?

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Chronic Myeloid Leukemia (CML) is the most probable diagnosis requiring immediate BCR::ABL1 testing and tyrosine kinase inhibitor therapy.

Most Likely Diagnosis

The clinical presentation of prolonged high-grade fever, severe anemia (Hb 6.5 g/dL), marked leukocytosis (WBC 25 × 10⁹/L), and thrombocytosis in a 13-year-old strongly suggests Chronic Myeloid Leukemia (CML), which must be confirmed with BCR::ABL1 fusion gene testing. 1, 2

The constellation of findings is highly characteristic:

  • Persistent fever can be a presenting feature of myeloproliferative disorders 3
  • Severe anemia requiring transfusions combined with leukocytosis and thrombocytosis indicates a clonal hematologic malignancy rather than reactive thrombocytosis
  • Thrombocytosis with leukocytosis in this context is pathognomonic for CML, as reactive thrombocytosis rarely presents with such marked leukocytosis 1, 2

Critical Diagnostic Steps

Order BCR::ABL1 fusion gene testing immediately - this is the definitive diagnostic test for CML 1, 2. The recent literature emphasizes that BCR::ABL1 testing should be performed early in any child with unexplained thrombocytosis, especially when accompanied by leukocytosis 2.

Additional required workup:

  • Peripheral blood smear (looking for left shift, basophilia, granulocytic hyperplasia)
  • Bone marrow biopsy with cytogenetics
  • Philadelphia chromosome analysis
  • Molecular quantification of BCR::ABL1 transcript levels

Why Not Secondary Thrombocytosis?

Secondary (reactive) thrombocytosis is common in children (3-13% of hospitalized patients) 4, 5, but this case has critical distinguishing features:

  • Reactive thrombocytosis is typically mild (<700 × 10⁹/L) and temporary 4
  • It rarely causes severe anemia requiring multiple transfusions
  • The three-month duration with persistent fever despite normal routine investigations argues against infection or inflammation
  • The combination of severe anemia + leukocytosis + thrombocytosis is not consistent with reactive processes 1

Immediate Treatment Protocol

Phase 1: Cytoreduction and Stabilization

Begin hydroxyurea immediately for cytoreduction while awaiting BCR::ABL1 results 1:

  • Prevents tumor lysis syndrome
  • Reduces leukocyte burden
  • Stabilizes platelet counts

Supportive measures 1:

  • Aggressive IV hydration
  • Allopurinol prophylaxis (tumor lysis prevention)
  • Continue transfusion support as needed
  • Monitor for leukostasis symptoms (though less likely at WBC 25 × 10⁹/L)

Phase 2: Definitive Therapy

Start imatinib (first-line tyrosine kinase inhibitor) once BCR::ABL1 is confirmed 1, 2:

  • Imatinib is the standard first-line therapy for pediatric CML
  • Expect complete cytogenetic response within 4 months 2
  • The prognosis is excellent with modern TKI therapy - CML in children is curable 1

Critical Pitfall to Avoid

Do not misdiagnose as essential thrombocythemia (ET) - a recent case report 2 describes a child initially misdiagnosed with ET and treated with hydroxyurea and aspirin without response. The key differentiator is that ET presents with isolated thrombocytosis only, whereas this patient has the triad of anemia, leukocytosis, and thrombocytosis.

Alternative Consideration: Acute Myeloid Leukemia (AML)

If BCR::ABL1 is negative, consider AML 6:

  • Hyperleukocytosis (though typically defined as WBC >100 × 10⁹/L) can occur in AML
  • However, AML typically presents with thrombocytopenia, not thrombocytosis
  • AML would require intensive chemotherapy followed by possible allogeneic stem cell transplant 6

The presence of thrombocytosis makes CML far more likely than AML in this clinical scenario.

References

4
Research

Thrombocytosis in children.

Minerva pediatrica, 2011

5
Research

Thrombocytosis in childhood.

Seminars in thrombosis and hemostasis, 1995

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