Leukocytosis

Background

• Leukocytosis is an increased white blood cell (WBC) count, with specific cutoffs based on a patient's age; in adults, leukocytosis is typically defined as WBC count > 11 × 10⁹/L.
• Leukocytes include granulocytes (neutrophils, eosinophils, and basophils), monocytes, and lymphocytes (B cells, T cells, and natural killer cells). Typical cell count cutoffs in adults for different types of leukocytosis include:
  • neutrophilia > 7-7.7 × 10⁹/L
  • eosinophilia > 0.5-1.5 × 10⁹/L
  • basophilia > 0.1 × 10⁹/L
  • monocytosis > 0.8-1.0 × 10⁹/L
  • lymphocytosis > 3.5-4.5 × 10⁹/L
• Primary (monoclonal) leukocytosis is an increased WBC count resulting from proliferation of a primary malignant WBC clone, for example in leukemia, lymphoma, or myeloproliferative neoplasm. Secondary (reactive or polyclonal) leukocytosis is an increased WBC count resulting from polyclonal proliferation of WBCs in response to infection, inflammatory disease, or malignancy.
• Leukocytosis can be acute or chronic. Reviewing prior blood work will help distinguish between the two.

Table 1. Other Relevant Definitions

Evaluation

• Important goals:
  • Evaluate patient for primary vs. reactive leukocytosis.
  • Evaluate patient for leukostasis.
    • Leukostasis is an oncologic emergency with risk of life-threatening cerebral infarcts, cerebral hemorrhage, or pulmonary insufficiency.
    • Leukostasis is caused by extreme elevations in WBC count (> 100-400 × 10⁹/L)
    • Leukostasis occurs more often in patients with hematological malignancy (especially acute myeloid leukemia).
• In patients with neutrophilia:
  • Look for reactive causes, including infection, chronic inflammation, smoking, stress, obesity, drugs (for example corticosteroids, beta-agonists, lithium, or epinephrine), endocrine disorders (such as hypercortisolism, thyroid storm, pre-eclampsia), splenectomy, bone marrow stimulation, and nonhematologic malignancy, and rarely in inherited disorders (check for family history of neutrophilia).
  • If no reactive cause identified, screen for clonal causes (myeloproliferative disorders such as chronic myeloid leukemia and or neutrophilic leukemia) using morphology and cytogenetics of peripheral blood and bone marrow, with a particular focus on BCR-ABL fusion gene and CSF3R mutations.
• In patients with monocytosis:
  • Look for reactive causes, including viral or bacterial infection, corticosteroids, malignancy, postsplenectomy state, autoimmune disorders (such as inflammatory bowel disease or sarcoidosis), and vasculitides.
  • If no reactive cause identified, screen for clonal cause (such as monocytic leukemia, chronic myelomonocytic leukemia, and mastocytosis) using morphology and cytogenetics of peripheral blood and bone marrow, with a particular focus on BCR-ABL fusion gene and PDGFRA, PDGFRB, or FGFR1 gene rearrangements.
• In patients with lymphocytosis:
  • Look for reactive causes, including viral, bacterial, or parasitic infection, vaccinations, connective tissue disease, and smoking.
  • If no reactive cause identified, screen for clonal cause using flow cytometric immunophenotyping of peripheral blood to identify possible lymphoproliferative disorder. Diagnosis may require bone marrow biopsy and molecular genetic analysis.
• In patients with eosinophilia:
  • Look for evidence of organ system involvement.
  • Look for reactive causes, including allergies (most common cause in Western countries), tissue-invasive parasites (most common cause in developing countries), and drug reactions (including cephalosporins, quinine, quinolones, antiseizure medications, semisynthetic penicillins, allopurinol, nonsteroidal anti-inflammatory drugs [NSAIDs]).
  • If no reactive cause identified, screen for clonal cause using morphology and cytogenetics of peripheral blood and bone marrow, with a particular focus on FIP1L1-PDGRA, PDGFRA, PDGFRB, or FGFR1 gene rearrangements and PCM1-JAK2 fusion gene.
• Basophilia is rare and should prompt testing for myeloproliferative neoplasm when present.

Management

• Management of leukocytosis, when necessary, varies according to underlying cause.
• For patients with signs and symptoms of leukostasis, perform leukapheresis to quickly reduce WBC burden (Strong recommendation).
• Prophylactic leukapheresis is generally not indicated for patients without signs or symptoms of leukostasis, and decision for apheresis should be individualized (Weak recommendation).