Can fever be seen in patients with hematological cancer, especially those with thrombocytosis and leukocytosis?

Fever in Hematological Malignancies with Thrombocytosis and Leukocytosis

Yes, fever is a common presentation in patients with hematological malignancies, including those with thrombocytosis and leukocytosis, and can be due to both infectious and non-infectious causes. 1

Causes of Fever in Hematological Malignancies

Infectious Causes

• Bacterial infections (most common initial cause)
  • Gram-positive pathogens: Coagulase-negative staphylococci, S. aureus, viridans group streptococci, enterococci 1
  • Gram-negative pathogens: E. coli, Klebsiella, Enterobacter species, Pseudomonas aeruginosa 1
• Fungal infections (typically later in disease course)
  • Candida species (especially with gastrointestinal mucositis)
  • Aspergillus species (with prolonged neutropenia) 1
• Viral infections
  • Herpes simplex virus, varicella zoster virus
  • Respiratory viruses (RSV, parainfluenza, influenza) 1

Non-Infectious Causes

• The underlying malignancy itself (tumor fever) 2
• Paraneoplastic syndromes
• Medication reactions
• Blood product transfusions
• Tumor lysis syndrome
• Thrombophlebitis

Risk Factors for Fever in Hematological Malignancies

• Advanced or refractory disease 1
• Neutropenia (especially when <100/mcL) 1
• Multiple lines of prior cytotoxic or immunosuppressive therapy 1
• Anatomic factors (tumor necrosis, obstruction) 1
• Disruption of mucosal barriers 1
• Malnutrition 1
• Presence of indwelling catheters 1

Diagnostic Approach

1. Complete blood count with differential

   • Document degree of leukocytosis, thrombocytosis, and presence of neutropenia
   • Examine peripheral smear for abnormal cells 3

2. Blood cultures (before antibiotic administration)

   • At least two sets from different sites
   • Include cultures from all vascular access devices

3. Imaging studies

   • Chest X-ray to rule out pulmonary infection
   • CT scan of chest if respiratory symptoms are present 1
   • Consider abdominal imaging if no localizing symptoms are present 1

4. Additional testing based on symptoms

   • Urinalysis and urine culture
   • Stool studies if diarrhea present
   • Skin lesion assessment
   • CSF analysis if neurological symptoms present

Management Algorithm

1. Initial assessment:

   • Determine if patient is hemodynamically stable
   • Assess for signs of sepsis or septic shock 1
   • Evaluate neutrophil count (risk increases significantly when <500/mcL) 1

2. Immediate management:

   • Start empiric broad-spectrum antibiotics immediately if neutropenic
   • For non-neutropenic patients with stable vital signs, complete diagnostic workup before starting antibiotics

3. Antibiotic selection:

   • For high-risk patients (neutropenia expected >7 days, unstable vital signs):
     • Monotherapy with antipseudomonal beta-lactam (cefepime, piperacillin-tazobactam, or carbapenem) 1
     • Consider adding vancomycin if clinically septic, suspected catheter-related infection, or known colonization with resistant gram-positive organisms 1

4. Reassessment after 48-72 hours:

   • If fever persists but patient is clinically stable, continue same antibiotics 1
   • If clinical deterioration occurs, modify antibiotics based on culture results or clinical assessment
   • Consider adding antifungal therapy if fever persists beyond 96 hours in high-risk patients 1

5. Duration of therapy:

   • Continue antibiotics until neutrophil recovery (>500/mcL) and resolution of fever 1
   • For patients with persistent neutropenia and resolution of fever, consider continuing antibiotics throughout neutropenic period 1

Special Considerations with Thrombocytosis and Leukocytosis

Patients with hematological malignancies presenting with thrombocytosis and leukocytosis may have:

1. Paraneoplastic inflammatory response

   • Some tumors produce cytokines (IL-6, G-CSF) that can cause leukocytosis and thrombocytosis 2
   • This can be associated with tumor fever that may not respond to antibiotics

2. Increased risk of thrombotic complications

   • Monitor for signs of thrombosis, especially with extreme thrombocytosis
   • Consider prophylactic anticoagulation if no contraindications

3. Differentiation syndrome in AML

   • Can present with fever, leukocytosis, and respiratory symptoms
   • Requires prompt recognition and treatment with corticosteroids 4

Pitfalls to Avoid

1. Delaying antibiotic therapy in neutropenic patients

   • Mortality increases with delays beyond 3 days of fever 5

2. Attributing all fevers to infection

   • Remember non-infectious causes, especially in patients with persistent fever despite appropriate antibiotics 6

3. Overuse of vancomycin

   • Adding vancomycin empirically for persistent fever alone is not recommended 1

4. Premature discontinuation of antibiotics

   • Continue antibiotics throughout neutropenic period in high-risk patients 1

5. Failure to consider fungal infections

   • Consider adding antifungal therapy for persistent fever beyond 96 hours in high-risk patients 1

By following this systematic approach, clinicians can effectively manage fever in patients with hematological malignancies presenting with thrombocytosis and leukocytosis, improving outcomes and reducing mortality.