Leukocytosis Evaluation and Management

Causes of Leukocytosis

• Fungal infections, Kawasaki disease, acute leukemias (including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)), chronic leukemias (including chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL)), myeloproliferative disorders, lymphoproliferative disorders, and hemophagocytic lymphohistiocytosis can cause leukocytosis, as reported by the National Comprehensive Cancer Network, American Heart Association, American Society of Hematology, European Society for Medical Oncology, and European Hematology Association 1, 2, 3, 4, 5, 6

Clinical Presentation and Evaluation

• Hepatosplenomegaly, lymphadenopathy, or unexplained bleeding/bruising raise suspicion for hematologic malignancy, and evaluation for signs and symptoms of infection is recommended, as stated by the National Comprehensive Cancer Network and American College of Physicians 1, 2
• Extremely elevated WBC counts, abnormal cell morphology, or accompanying cytopenias should prompt urgent hematology consultation, as stated by the American Society of Hematology 3

Management and Prognosis

• Determining which WBC subpopulation is increased (including neutrophilia, lymphocytosis, monocytosis, eosinophilia, or basophilia) is crucial to guide further diagnosis and management, with a strength of evidence level of high, as recommended by the American Society of Hematology 7
• Reviewing peripheral blood smear for presence of immature cells, abnormal cell morphology, and blasts is crucial for diagnosing acute leukemia, with a high level of evidence, as suggested by the National Comprehensive Cancer Network 7
• The World Health Organization classifies leucopenia as mild (1,000-1,500/μL), moderate (500-1,000/μL), or severe (<500/μL), which requires urgent attention, and the diagnosis of leucopenia should involve reviewing previous hemograms to understand the temporal evolution of the condition, as recommended by the World Health Organization and European Hematology Association 8
• The following table summarizes the recommended treatments for different types of leukemia:

• Treating the underlying cause of leukocytosis rather than the elevated white blood cell count itself is recommended, with specific interventions determined by the etiology and severity of the condition, with a strength of evidence level of high, as stated by the American Society of Hematology 7
• Induction chemotherapy with cytarabine and an anthracycline is recommended for the treatment of acute leukemia, with a strength of evidence of high, as recommended by the National Comprehensive Cancer Network 7, 9
• Tyrosine kinase inhibitors (e.g., imatinib) are recommended for Chronic Myelogenous Leukemia (CML), with a strength of evidence of high, as recommended by the American College of Physicians 10
• Regular complete blood counts with differential and bone marrow examination for suspected primary bone marrow disorders are recommended to monitor response to treatment, with a high level of evidence, as suggested by the European Society for Medical Oncology 11
• Targeted antimicrobial therapy based on suspected or confirmed pathogens is recommended for the treatment of infections, with a strength of evidence of high, as recommended by the Infectious Diseases Society of America 7, 9
• Treatment decisions should be based on disease stage, previous treatments, and genetic factors, such as the presence of del(17p) or del(11q), with a strength of evidence level of high, as recommended by the American Society of Clinical Oncology 12
• Identifying and treating the underlying infection, and using appropriate antimicrobial therapy based on suspected source, is recommended to manage leukocytosis caused by infections, with a strength of evidence level of high, as recommended by the American College of Physicians 7
• Leukocytosis with eosinophilia (>500 cells/μL) may indicate allergic reactions, parasitic infections, or certain malignancies, as suggested by the American Academy of Allergy, Asthma, and Immunology 13
• Hospitalization, initiation of broad-spectrum antibiotics, blood cultures, and consideration of granulocyte colony-stimulating factors (such as filgrastim) are recommended for patients with severe leucopenia, with a strength of evidence level of high, as recommended by the National Comprehensive Cancer Network 8
• Severe leucopenia (<1000/μL) represents an immediate threat to life and requires urgent search for the underlying cause, as stated by the European Hematology Association, with a high level of evidence 8
• Early initiation of broad-spectrum antibiotics is crucial to reduce mortality in patients with fever and neutropenia, as recommended by the Infectious Diseases Society of America, with a strength of evidence level of high 8