What is the management approach for a patient with chronically elevated White Blood Cell (WBC) and lymphocyte counts?

From the Guidelines

The management of a patient with chronically elevated White Blood Cell (WBC) and lymphocyte counts should prioritize a watchful waiting approach for asymptomatic patients, unless specific criteria for active disease are met, as outlined in the guidelines for chronic lymphocytic leukemia (CLL) 1. The approach to managing chronically elevated WBC and lymphocyte counts involves a comprehensive diagnostic evaluation to determine the underlying cause, which could include chronic lymphocytic leukemia (CLL), lymphoma, reactive lymphocytosis due to infections, autoimmune disorders, or medication effects. For patients with CLL, the decision to initiate treatment depends on the presence of active disease, defined by criteria such as evidence of progressive marrow failure, massive or progressive splenomegaly, massive nodes, progressive lymphocytosis, autoimmune anemia or thrombocytopenia, or constitutional symptoms 1. Key considerations in the management of CLL include:

• Monitoring without therapy for asymptomatic patients with early-stage disease (Rai 0, Binet A) unless there is evidence of disease progression 1.
• Initiating treatment for patients at intermediate or high risk, or those with symptomatic disease, using therapies such as chemoimmunotherapy regimens, BTK inhibitors, or BCL-2 inhibitors.
• Regular monitoring with complete blood counts every 3-6 months for asymptomatic patients to assess for signs of disease progression. This approach prioritizes the patient's quality of life and minimizes unnecessary treatment, while ensuring timely intervention for those with active or progressive disease.

From the Research

Management Approach for Chronically Elevated WBC and Lymphocyte Counts

The management approach for a patient with chronically elevated White Blood Cell (WBC) and lymphocyte counts involves several steps:

• Confirming the complete blood cell count and the WBC differential 2
• Examining the peripheral blood smear to confirm the automated blood cell differential or affirm the manual differential performed on the peripheral blood smear 2
• Separating the leukocytosis into a myeloid versus a lymphoid process 2
• Distinguishing a reactive lymphoid proliferation from a lymphoproliferative disorder by examining lymphocyte morphology for pleomorphic lymphocytes versus a monomorphic population 2

Potential Causes of Chronically Elevated WBC and Lymphocyte Counts

Potential causes of chronically elevated WBC and lymphocyte counts include:

• Malignant causes, such as leukemia 3, 4
• Nonmalignant causes, such as infection, certain medications, asplenia, smoking, obesity, and chronic inflammatory conditions 3
• Reactive lymphoid proliferations, which can be distinguished from lymphoproliferative disorders by examining lymphocyte morphology 2
• Myeloid leukemoid reactions, which can be caused by infections and show activated neutrophil changes on morphology 2

Diagnostic Tests and Procedures

Diagnostic tests and procedures that may be used to evaluate chronically elevated WBC and lymphocyte counts include:

• Complete blood count with peripheral smear 3, 2
• Flow cytometry to confirm and characterize lymphoproliferative disorders 2
• Molecular studies to initiate in select cases 2
• Bone marrow examination to confirm and characterize myeloid malignancies 2

Association with Other Factors

Chronically elevated WBC counts have been associated with other factors, including:

• Impulsivity-related traits, such as impulsiveness and excitement-seeking 5
• Smoking and body mass index, which can mediate the association between impulsivity and chronic inflammation 5