These can raise concern for an underlying hematologic malignancy, but can also be a normal variation or due to another cause. The basic elements of evaluation include personal history and physical examination; family history; review of medication, supplements, and other drug use; complete blood count and differential; and peripheral blood smear.

Lymphopenia and Neutropenia

Lymphopenia can occur as a response to steroids, other medications, bacterial, viral infections. Chronic low lymphocytes should prompt consideration of underlying immunodeficiency.

• Immunodeficiency disorder
• Infections: HIV, TB, hepatitis, typhoid, malaria, measles, fungal
• steroids, RTX, immunosuppressants
• Systemic disease (autoimmune, endocrine)
• Alcohol, zinc deficiency, protein-losing enteropathy

Neutropenia can result from impaired marrow production, immune mediated destruction, or cellular redistribution to the spleen (for example in portal hypertension). Severe neutropenia is defined as ANC < 0.5.

• Benign ethnic neutropenia (Duffy-null neutropenia) is a mild neutropenia (1-1.5) driven by the absence of the Duffy antigen (receptor for Falciparum ovale) --> hence more common amongst sub-Saharan African or Middle-Eastern patients. Myeloid progenitors are mildly reduced, but maturation and function are normal. It is clinically insignificant w/o increased risk of infections.
• Medication-induced neutropenia results from impaired granulopoiesis or an antibody-mediated destructive process. It is usually seen in the first 3 months of drug initiation as is usually reversible. Most often in patients >50 yrs age. Can involve fever, oral ulcerations. Remove the drug, and the patient will get better within 1-3 weeks. G-CSF can be considered to shorten recovery time, and can be used in patients with neutropenia and active infection.
• Nutritional deficiencies such as folate, B12 can cause neutropenia along with macrocytic anemia and thrombocytopenia. Copper deficiency as well.
• Autoimmune conditions like lupus, rheumatoid arthritis (e.g. Felty syndrome), etc.
• Other: Sepsis, HIV, EBV, aplastic anemia

Neutrophilia, Lymphocytosis, and Monocytosis

These are often reactive to infection or general inflammation.

Lymphocytosis occurs with many viral processes such as acute EBV. Monoclonal B cell lymphocytosis is a premalignant condition (--> CLL) with a monoclonal population of B lymphocytes <5 that does not meet criteria for CLL or other LPD.

Neutrophilia can be from cigarette smoking, bacterial infection, medications such as steroids, and obesity (especially in women).

Monocytosis can be from infections such as TB, but can represent an underlying hematopoietic stem cell disorder or CMML especially with other cytopenias.

References

1. MKSAP 19