How to diagnose an acute infection in a patient with chronic myelomonocytic leukemia (CMML) and elevated white blood cell (WBC) count?

Differentiating Acute Infection in Patients with Chronic Myelomonocytic Leukemia and Elevated WBC

In patients with chronic myelomonocytic leukemia (CMML) and elevated white blood cell count, the diagnosis of acute infection requires a comprehensive evaluation of clinical symptoms, inflammatory markers, and specific diagnostic tests, as baseline leukocytosis can mask typical infectious signs.

Clinical Assessment

• The presence of fever (temperature >100°F/37.8°C, >2 readings of >99°F/37.2°C, or an increase of 2°F/1.1°C over baseline) should prompt immediate evaluation for infection, even in patients with baseline leukocytosis 1
• New-onset or worsening respiratory symptoms (shortness of breath, cough, hypoxemia) may indicate pneumonia and require prompt assessment including pulse oximetry and chest imaging 1
• Careful assessment for other signs of infection such as dysuria, gross hematuria, new or worsening urinary incontinence for UTI, or localized pain and swelling for soft tissue infections 1

Laboratory Evaluation

• Complete blood count with manual differential to assess for:

  • Left shift (percentage of band neutrophils or metamyelocytes >6%, or total band neutrophil count >1,500 cells/mm³) which strongly suggests bacterial infection even in the setting of baseline leukocytosis 1
  • Significant increase from baseline WBC count, particularly with neutrophilia (>90% neutrophils) 1
  • New or worsening cytopenias that may indicate bone marrow involvement with infection 1

• Inflammatory markers:

  • C-reactive protein (CRP) and procalcitonin (PCT) are valuable for detecting bacterial infections in leukemia patients 1
  • These markers can help distinguish infection from disease progression when clinical presentation is ambiguous 1

Specific Diagnostic Tests

• For suspected pneumonia:

  • Chest X-ray or CT scan (CT is more sensitive) to evaluate for infiltrates 1
  • Respiratory samples (sputum, nasopharyngeal aspirate) for culture and PCR testing 1
  • Blood cultures, urinary antigens for Legionella and Pneumococcus 1
  • Serum galactomannan and beta-D-glucan if fungal infection is suspected 1

• For suspected bloodstream infection:

  • At least two sets of blood cultures before starting antibiotics 1
  • Consider removing and replacing central venous catheters if present and clinically indicated 1

• For suspected urinary tract infection:

  • Urinalysis for leukocyte esterase and nitrite by dipstick 1
  • Urine culture only in symptomatic patients (avoid testing in asymptomatic patients) 1

Diagnostic Challenges and Pitfalls

• Baseline monocytosis in CMML can mask typical infectious leukocytosis patterns, making trend changes more important than absolute values 1, 2
• CMML patients may have blunted febrile responses due to age or medications, so even low-grade fevers should be taken seriously 1
• Differentiate between disease progression/transformation and infection, as both can present with increasing WBC counts and constitutional symptoms 1
• Be aware that CMML patients may have concurrent inflammatory or autoimmune conditions (up to 20%) that can mimic infection 3

Management Approach

• For patients with clinical signs of infection and laboratory evidence (left shift, elevated inflammatory markers):

  • Initiate empiric broad-spectrum antibiotics promptly while awaiting culture results 1
  • Consider the local patterns of antimicrobial resistance when selecting empiric therapy 1
  • Avoid fluoroquinolones if possible due to potential drug interactions with medications commonly used in leukemia treatment 1

• For patients with fever but unclear evidence of infection:

  • Close monitoring with serial clinical assessments and laboratory tests 1
  • Consider empiric antibiotics if neutropenic (absolute neutrophil count <500/mm³) 1
  • Evaluate for non-infectious causes of fever including disease progression 2

Special Considerations

• Patients with CMML may be at higher risk for atypical infections, particularly if previously treated with hypomethylating agents or other therapies 1
• Consider tuberculosis screening in patients with risk factors and unexplained symptoms 1
• Prophylactic antimicrobials are not routinely recommended for CMML patients unless they have received agents associated with increased infection risk (e.g., corticosteroids, purine analogues) 1

By systematically evaluating clinical symptoms, laboratory markers (particularly left shift and inflammatory markers), and using appropriate diagnostic tests, clinicians can effectively differentiate between baseline CMML-related leukocytosis and acute infection requiring prompt intervention.