What is the appropriate workup and treatment for a patient with leukocytosis (elevated White Blood Cell (WBC) count) and monocytosis (high monocyte count)?

Workup for Elevated WBC Count and Monocytosis

A patient with leukocytosis and monocytosis (994 cells/μL) requires a comprehensive diagnostic evaluation to rule out hematologic malignancies, particularly chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). 1

Initial Diagnostic Workup

• Complete blood count with differential, platelets, peripheral blood smear examination 1, 2
• Comprehensive chemistry profile, uric acid, lactate dehydrogenase (LDH) 1
• Bone marrow aspiration and biopsy with cytogenetics (karyotype ± FISH) 1
• Molecular analyses (including KIT, FLT3-ITD, NPM1, CEBPA mutations for suspected AML) 1
• Immunophenotyping by flow cytometry to characterize abnormal cells 1
• Conventional cytogenetic analysis to detect clonal abnormalities 1
• Molecular assays to exclude bcr/abl fusion gene (to rule out CML) 1
• Testing for PDGFRA and PDGFRB rearrangements (especially if eosinophilia is present) 1

Specific Diagnostic Criteria for CMML

If CMML is suspected, confirm the following diagnostic criteria:

• Persistent peripheral blood monocytosis >1×10⁹/L 1
• No Philadelphia chromosome or BCR-ABL1 fusion gene 1
• No rearrangement of PDGFRA or PDGFRB 1
• Less than 20% blasts in peripheral blood and bone marrow 1
• At least one of the following: 1
  • Dysplasia in one or more cell lines
  • Acquired clonal cytogenetic or molecular genetic abnormality
  • Persistence of monocytosis for at least 3 months with exclusion of other causes

Additional Testing Based on Clinical Presentation

• Coagulation studies (PT, PTT, fibrinogen) if bleeding symptoms or if considering treatment that may affect coagulation 1
• HLA typing for patients under 65 years who might be candidates for hematopoietic stem cell transplantation 1
• Serum erythropoietin levels if anemia is present (Hb ≤10 g/dL) 1
• Lumbar puncture if neurologic symptoms are present (particularly in cases of suspected acute leukemia) 1
• Imaging studies (CT, MRI) if extramedullary disease is suspected 1

Management Considerations Based on Diagnosis

For Benign Leukocytosis

• Rule out reactive causes: infections, inflammation, physical/emotional stress, medications (corticosteroids, lithium, beta-agonists) 2, 3
• Monitor complete blood counts periodically to ensure stability 2

For CMML

Treatment strategy depends on disease phenotype:

• For myelodysplastic CMML (MD-CMML) with <10% blasts: supportive care, erythropoietic stimulating agents if anemic 1
• For MD-CMML with ≥10% blasts: hypomethylating agents (5-azacytidine or decitabine) 1
• For myeloproliferative CMML (MP-CMML) with low blast count: hydroxyurea for cytoreduction 1
• For MP-CMML with high blast count: intensive chemotherapy followed by allogeneic stem cell transplantation when possible 1

For AML

• Standard induction therapy typically includes cytarabine with an anthracycline (idarubicin or daunorubicin) 1
• Clinical trials should be considered when available 1
• Molecular testing results may guide specific therapeutic interventions (e.g., midostaurin for FLT3-mutated AML) 1

Emergency Management for Severe Leukocytosis

If WBC count >100,000/μL (hyperleukocytosis):

• Immediate aggressive IV hydration (2.5-3 liters/m²/day) 4
• Monitor for and prevent tumor lysis syndrome with allopurinol or rasburicase 4
• Consider hydroxyurea (50-60 mg/kg/day) for rapid cytoreduction 4
• In cases of leukostasis with organ dysfunction, consider leukapheresis 4, 5
• Maintain platelet counts above 30-50 × 10⁹/L to prevent bleeding complications 4

Common Pitfalls to Avoid

• Don't assume all monocytosis is malignant; persistent monocytosis requires at least 3 months of follow-up to meet CMML criteria 1
• Don't miss evaluation for reactive causes of monocytosis (infections, inflammatory conditions) 2, 6
• Don't delay treatment in cases of hyperleukocytosis (>100,000/μL), which represents a medical emergency 3, 5
• Don't forget to evaluate for tumor lysis syndrome in patients with high WBC counts 4, 5
• Don't overlook the need for molecular testing, which is increasingly important for diagnosis and treatment selection 1