What is the next step in managing a patient with leukocytosis and neutrophilia?

Management of Persistent Leukocytosis and Neutrophilia

The next step in managing this patient with persistent leukocytosis and neutrophilia should be a bone marrow aspiration and cytogenetic analysis to rule out chronic myelogenous leukemia (CML) or other myeloproliferative disorders.

Diagnostic Evaluation

The patient presents with concerning laboratory findings:

• Persistent leukocytosis: WBC counts of 14.7,14.1, and now 15.5 (consistently elevated)
• Progressive neutrophilia: ANC increasing from 8.81 to 9.09 to 10.45
• Elevated inflammatory markers: ESR 31 and CRP 43.1
• Low rheumatoid factor: <10

These findings warrant a systematic approach to diagnosis:

1. Bone marrow examination:

   • Essential for diagnosing CML and other myeloproliferative disorders
   • Should include cytogenetics and BCR-ABL transcript measurement by QPCR 1
   • If bone marrow collection is not feasible, FISH on peripheral blood using dual probes for BCR and ABL genes is acceptable 1

2. Additional laboratory tests:

   • Complete metabolic panel to assess organ function
   • Blood cultures if febrile
   • Peripheral blood smear examination for cell morphology

Differential Diagnosis

Malignant Causes

• Chronic Myelogenous Leukemia (CML): Most concerning given persistent leukocytosis with neutrophilia
• Other myeloproliferative disorders
• Leukemoid reaction

Non-Malignant Causes

• Infection (bacterial more likely with neutrophilia)
• Inflammatory conditions
• Medication effect
• Physiologic stress response
• Smoking or obesity 2

Management Algorithm

1. Initial Assessment:

   • Evaluate for signs of infection (fever, specific symptoms)
   • Review medication history for drugs that can cause leukocytosis
   • Assess for underlying inflammatory conditions

2. Immediate Testing:

   • Bone marrow aspiration with cytogenetics
   • BCR-ABL transcript measurement by QPCR
   • Peripheral blood smear

3. If CML is confirmed:

   • Initiate appropriate tyrosine kinase inhibitor (TKI) therapy
   • Monitor BCR-ABL transcript levels every 3 months 1
   • Follow-up bone marrow cytogenetics at 6 months from initiation of therapy 1

4. If infection is suspected:

   • Obtain appropriate cultures
   • Initiate empiric antibiotics if febrile or clinically unstable 1
   • Consider imaging studies based on clinical presentation 3

Important Considerations

• Persistent leukocytosis with neutrophilia is associated with high mortality rates and should not be overlooked 4, 5
• The progressive increase in neutrophil count is particularly concerning for a myeloproliferative disorder
• While infection can cause neutrophilia, the persistent and progressive nature of the counts suggests a potential underlying hematologic disorder
• Elevated CRP (43.1) may be seen in both infection and systemic inflammatory conditions, but does not reliably distinguish between them 6

Pitfalls to Avoid

• Do not assume infection without evidence: While infection is a common cause of leukocytosis, the persistent nature of the elevated counts warrants investigation for hematologic malignancy
• Do not delay bone marrow examination: Early diagnosis of CML significantly impacts treatment outcomes
• Do not attribute leukocytosis solely to inflammation: The progressive neutrophilia is concerning for a myeloproliferative disorder
• Do not dismiss normal temperature: Absence of fever does not exclude serious underlying pathology, especially in hematologic malignancies

The patient's persistent and progressive leukocytosis with neutrophilia requires prompt hematologic evaluation, as early diagnosis and treatment of potential myeloproliferative disorders can significantly impact morbidity and mortality.