What is the evaluation and treatment approach for monocytosis, an increase in monocytes (white blood cells)?

Evaluation and Management of Monocytosis

For an adult with monocytosis, confirm absolute monocyte count >1×10⁹/L with peripheral blood smear examination, then systematically exclude reactive causes (infections, inflammatory conditions) before pursuing bone marrow evaluation for persistent unexplained cases to rule out chronic myelomonocytic leukemia (CMML). 1, 2

Initial Laboratory Confirmation

• Verify absolute monocytosis (>1×10⁹/L) rather than relative monocytosis, as failing to distinguish between these leads to unnecessary workup 1, 2
• Obtain peripheral blood smear to assess monocyte morphology, presence of dysgranulopoiesis, promonocytes, blasts, and neutrophil precursors 1, 2
• Complete blood count with differential and comprehensive metabolic panel are essential baseline studies 1, 2

Systematic Evaluation for Reactive Causes

The vast majority of monocytosis cases are reactive and easily identified by clinical context 3. Focus your history and examination on:

Infectious Etiologies

• Chronic infections: tuberculosis, bacterial endocarditis, and other persistent bacterial infections 2
• Listeria monocytogenes: particularly critical in immunosuppressed patients presenting with neurological symptoms—requires immediate lumbar puncture 2
• Recovery phase from bone marrow suppression or acute infection 1

Inflammatory and Autoimmune Conditions

• Inflammatory bowel disease: Crohn's disease and ulcerative colitis commonly cause chronic monocyte elevation 2
• Adult-onset Still's disease: presents with marked leukocytosis (WBC >15×10⁹/L) including monocytosis 2
• Cardiovascular disease: atherosclerosis and coronary artery disease associate with elevated monocyte counts 2
• Tissue injury and chronic inflammation of any cause 2

Other Reactive Causes

• Solid tumors and recovery from chemotherapy 1
• Autoimmune disorders 1

Indications for Bone Marrow Evaluation

Proceed to bone marrow aspiration and biopsy when: 1, 2

• Monocytosis persists without identifiable reactive cause
• Peripheral smear shows dysplastic features, promonocytes, or blasts
• Additional cytopenias are present
• Splenomegaly or lymphadenopathy detected on examination 1

Bone Marrow Studies Must Include:

• Aspiration and biopsy to assess marrow cellularity, dysplasia, and blast percentage (including myeloblasts, monoblasts, and promonocytes) 1, 2
• Gomori's silver impregnation staining for fibrosis 1, 2
• Conventional cytogenetic analysis to exclude t(9;22) Philadelphia chromosome, BCR-ABL1 fusion gene, and t(5;12) translocations 1, 2
• Molecular testing for mutations commonly found in CMML (TET2, SRSF2, ASXL1, RAS) 1, 2

Management Based on Diagnosis

For Reactive Monocytosis

• Treat the underlying condition (infection, inflammation, autoimmune disorder) 2
• Monitor resolution of monocytosis with treatment of primary condition 1

For CMML (Myelodysplastic Type)

• <10% bone marrow blasts: Supportive therapy aimed at correcting cytopenias 1, 2
• ≥10% bone marrow blasts: Hypomethylating agents (5-azacytidine or decitabine) plus supportive therapy 1, 2

For CMML (Myeloproliferative Type)

• <10% blasts: Hydroxyurea as first-line cytoreductive therapy to control proliferative cells and reduce organomegaly 1, 2
• High blast count: Polychemotherapy followed by allogeneic stem cell transplantation when feasible 1, 2

For Both CMML Types

• Allogeneic stem cell transplantation should be considered in selected patients, ideally within clinical trials 1

Critical Pitfalls to Avoid

• Missing absolute vs. relative monocytosis: Always calculate absolute monocyte count, not just percentage 1, 2
• Attributing persistent monocytosis to benign causes without adequate investigation delays CMML diagnosis 2
• Skipping bone marrow evaluation in persistent unexplained monocytosis is the most critical error 1, 2
• Overlooking molecular testing to exclude specific myeloid neoplasms in persistent cases 2
• Ignoring Listeria in immunosuppressed patients: Monocytosis with neurological symptoms requires immediate lumbar puncture 2
• Misinterpreting transient post-treatment changes: Monocytosis during immune response initiation is typically not clinically significant 2

Special Consideration: Clonal Hematopoiesis

Recent evidence shows that monocytosis in older adults (≥60 years) frequently associates with clonal hematopoiesis (CH), occurring in 50.9% vs. 35.5% in age-matched controls 4. Persistent monocytosis over 4 years associates with even higher CH prevalence (63%) 4. While CH and monocytosis both occur with aging and don't necessarily reflect clonal monocytic proliferation, mutational spectra deviating from typical age-related CH (particularly multiple mutations or spliceosome mutations) require heightened attention for potential progression to myeloid malignancy 4.