How to manage a patient with leukocytosis, neutrophilia, lymphocytosis, eosinophilia, and basophilia?

Management of Leukocytosis with Neutrophilia, Lymphocytosis, Eosinophilia, and Basophilia

This patient requires immediate BCR-ABL1 fusion gene testing via PCR or cytogenetics to exclude chronic myeloid leukemia (CML), as the combination of basophilia and eosinophilia with leukocytosis is highly suggestive of a myeloproliferative neoplasm rather than a reactive process. 1

Immediate Diagnostic Priorities

The constellation of findings—leukocytosis (12.4 x10^9/L), neutrophilia (8.0 x10^9/L), lymphocytosis (2.6 x10^9/L), eosinophilia (0.8 x10^9/L), and basophilia (0.2 x10^9/L)—demands urgent evaluation for myeloproliferative neoplasms, particularly CML. 1

Critical First-Line Testing (Within 24-48 Hours)

• BCR-ABL1 fusion gene testing via PCR or cytogenetics is the definitive diagnostic test and must be performed immediately. 1
• Peripheral blood smear review to assess for immature myeloid cells (blasts, promyelocytes, myelocytes), dysplasia, and confirm the automated differential. 1, 2
• Serum tryptase and vitamin B12 levels are elevated in myeloproliferative variants and help distinguish neoplastic from reactive eosinophilia. 1
• Lactate dehydrogenase (LDH) correlates with disease burden in myeloproliferative disorders and has prognostic importance. 1

If BCR-ABL1 is Negative

• FISH or RT-PCR for tyrosine kinase fusion genes (PDGFRA, PDGFRB, FGFR1, PCM1-JAK2) should be ordered if BCR-ABL1 is negative but eosinophilia and basophilia persist. 1
• Bone marrow aspirate and biopsy with cytogenetic analysis (minimum 15 metaphases) is necessary to assess blast percentage and identify additional chromosomal aberrations. 1

Secondary Differential Considerations

Chronic Myelomonocytic Leukemia (CMML)

CMML should be considered if monocytosis is >1×10^9/L persistently, though the combination with basophilia and eosinophilia makes this less likely than CML. 1 The monocyte count in this patient (0.9 x10^9/L) is at the upper limit of normal, not meeting CMML criteria. 1

Adult-Onset Still's Disease (AOSD)

While AOSD can present with marked leukocytosis (often >15×10^9 cells/L with 50% having counts >20×10^9), it typically presents with striking neutrophilia without the basophilia and eosinophilia seen here. 3 AOSD should be considered only if the patient has fever, arthritis/arthralgia, sore throat, and characteristic salmon-pink rash. 3

Reactive Causes (Lower Priority Given This Presentation)

Reactive leukocytosis from infection, inflammation, medications (corticosteroids, lithium, beta agonists), physical stress, or emotional stress typically does not present with the combination of basophilia and eosinophilia. 4, 5 Allergic disorders and parasitic infections are the most common causes of reactive eosinophilia but would not explain the basophilia and overall pattern. 3

Risk Stratification

The presence of blast cells in peripheral blood or marrow indicates progression to acute leukemia with high mortality risk. 1 The peripheral smear must be examined urgently for blasts, as 10-19% blasts defines accelerated phase and ≥20% blasts defines blast phase disease. 3

White blood cell counts above 100×10^9/L represent a medical emergency due to risk of brain infarction and hemorrhage from hyperviscosity, though this patient's count (12.4×10^9/L) does not meet this threshold. 5

Management Algorithm

Step 1: Obtain BCR-ABL1 Testing and Peripheral Smear Review (24-48 Hours)

This is the most critical initial step. 1

Step 2: Immediate Hematology Referral If:

• BCR-ABL1 is positive 1
• Blasts are present on peripheral smear 1
• White blood cell count is extremely elevated (>100×10^9/L) 5
• Concurrent abnormalities in red blood cell or platelet counts suggest primary bone marrow disorder 5

Step 3: If BCR-ABL1 Negative, Proceed With:

• PDGFRA/PDGFRB/FGFR1 testing 1
• Bone marrow biopsy with cytogenetics 1
• Quantitative immunoglobulins including IgE (polyclonal elevation suggests chronic inflammation while monoclonal patterns suggest lymphoproliferative disorders) 1

Step 4: Rule Out Secondary Causes

• Medication review: Corticosteroids, lithium, beta agonists can cause leukocytosis. 4, 5
• Infection screening: Complete blood count with differential can double within hours after infection due to bone marrow storage pools. 4
• Parasitic infection workup: Strongyloidiasis is the most common parasitic cause of eosinophilia. 3
• Autoimmune/inflammatory conditions: Chronic inflammatory conditions can cause reactive leukocytosis. 4

Monitoring Strategy

For asymptomatic patients with mild, stable cytopenias awaiting test results, a watch-and-wait strategy with regular monitoring of blood counts every 3 months is appropriate. 6 However, given the concerning pattern of multiple cell line elevations, more frequent monitoring (weekly) is warranted until myeloproliferative neoplasm is excluded. 7

Watch for Signs of Disease Progression:

• Increasing lymphocytosis or lymphocyte doubling time <12 months 6
• Progressive decline in neutrophil count or absolute neutrophil count dropping below 0.5×10^9/L 6
• Development of constitutional symptoms (fever, night sweats, weight loss) 6
• Appearance of lymphadenopathy or splenomegaly 6
• Recurrent or severe infections 6

Common Pitfalls to Avoid

• Do not dismiss this as reactive leukocytosis without excluding myeloproliferative neoplasms, as the combination of basophilia and eosinophilia is highly specific for CML or other tyrosine kinase fusion disorders. 1
• Do not delay BCR-ABL1 testing while pursuing other workup, as this is the definitive diagnostic test. 1
• Avoid unnecessary bone marrow biopsies in patients with mild, stable cytopenias without other concerning features, but this patient's multi-lineage elevation warrants bone marrow examination if BCR-ABL1 is negative. 6, 1
• Do not attribute eosinophilia solely to allergies or parasites without excluding myeloid neoplasms when basophilia is also present. 3, 1