Initial Workup for Chronic Leukocytosis
The initial workup for chronic leukocytosis should include a complete blood count with differential, peripheral blood smear examination, bone marrow aspirate and biopsy, and cytogenetic/molecular testing to determine the underlying cause and guide appropriate management. 1, 2
Diagnostic Approach
Initial Laboratory Evaluation
- Complete blood count (CBC) with differential to quantify the degree of leukocytosis and identify which cell lineage is predominantly affected 1, 2
- Peripheral blood smear examination to assess cell morphology and identify abnormal cells 1, 3
- Chemistry profile including LDH, bilirubin, and renal function tests 1
- Serum protein electrophoresis to evaluate for monoclonal proteins 1
- Direct antiglobulin test (Coombs test) to assess for autoimmune hemolytic anemia 1
Advanced Testing
- Bone marrow aspirate and biopsy for morphologic assessment, particularly before initiating therapy 1
- Immunophenotyping by flow cytometry to characterize abnormal cells (e.g., CD5+, CD19+, CD20+, CD23+ pattern in CLL) 1
- Cytogenetic analysis with FISH to detect chromosomal abnormalities with prognostic significance 1
- Molecular studies for specific genetic markers (e.g., BCR-ABL for CML) 1, 4
Differential Diagnosis
Malignant Causes
- Chronic lymphocytic leukemia (CLL): Characterized by ≥5 × 10^9/L mature-appearing lymphocytes with specific immunophenotype 1
- Chronic myeloid leukemia (CML): Often presents with basophilia, immature granulocytes, and BCR-ABL fusion gene 1, 4
- Other lymphoproliferative disorders: Including mantle cell lymphoma, which requires differential diagnosis from CLL 1
Reactive Causes
- Infections (bacterial, viral)
- Chronic inflammatory conditions
- Physiologic stress responses
- Medication effects 2, 3
Specific Diagnostic Criteria
For Chronic Lymphocytic Leukemia
- Sustained lymphocytosis ≥5 × 10^9/L with predominance of small, mature lymphocytes 1
- Characteristic immunophenotype: CD5+, CD19+, CD20+ (low), CD23+, surface immunoglobulin (sIg) low, CD79b low, FMC7– 1
- Bone marrow biopsy not required for diagnosis but recommended before treatment initiation 1
For Chronic Myeloid Leukemia
- Leukocytosis with left-shifted granulocytic series
- Presence of Philadelphia chromosome or BCR-ABL fusion gene
- Elevated basophil count (>0.43 × 10^9/L) is a sensitive screening marker 1, 4
Imaging Studies
- Chest X-ray to evaluate for lymphadenopathy or other pulmonary pathology 1
- Abdominal ultrasound or CT scan to assess for hepatosplenomegaly and intra-abdominal lymphadenopathy 1
Risk Stratification
For CLL
- Cytogenetic abnormalities by FISH have significant prognostic value 1
- Del(17p) or p53 mutations indicate poor prognosis and altered treatment approach 1
- Clinical staging using Binet or Rai systems helps determine prognosis and treatment needs 1
Treatment Approach
For CLL
- Early-stage disease (Binet A/B without symptoms, Rai 0-II without symptoms): Watch and wait strategy with monitoring every 3-6 months 1
- Advanced or symptomatic disease: Treatment options based on patient fitness, comorbidities, and cytogenetic profile 1
- For fit patients: Fludarabine, cyclophosphamide, and rituximab (FCR) combination 1
- For patients with comorbidities: Chlorambucil or reduced-dose purine analog therapy 1
For CML
- Initial workup should include bone marrow aspirate and biopsy with cytogenetics 1
- Tyrosine kinase inhibitors are the standard first-line therapy 1
Clinical Pearls and Pitfalls
- Leukostasis is a rare but potentially life-threatening complication of extreme leukocytosis (typically WBC >100 × 10^9/L) requiring urgent intervention 5
- Not all patients with chronic leukocytosis require immediate treatment; decision depends on disease type, stage, and symptoms 1
- Careful differential diagnosis between CLL and other lymphoproliferative disorders is essential as treatment approaches differ significantly 1
- Monitoring for disease progression is crucial in patients under observation (watch and wait strategy) 1