What is the management plan for a patient with severe neutropenia (Absolute Neutrophil Count (ANC) <200 cells per microliter) and a history of chemotherapy, radiation therapy, or chronic medical conditions?

Management of Severe Neutropenia (ANC <200 cells/µL)

For patients with ANC <200 cells/µL, immediately initiate broad-spectrum antibiotics if any fever is present (temperature ≥38.0°C), start G-CSF (filgrastim) 5 μg/kg/day subcutaneously, implement antimicrobial prophylaxis, and monitor closely with daily complete blood counts until ANC recovers to ≥500 cells/µL. 1, 2

Immediate Assessment and Risk Stratification

• Check temperature immediately - any fever in a patient with ANC <200 constitutes a medical emergency requiring same-day antibiotics 2
• Assess hemodynamic stability, as unstable patients require monitoring every 2-4 hours and urgent infectious disease consultation 1, 2
• Obtain baseline CBC with differential, blood cultures (if febrile), urinalysis and culture, and chest imaging if respiratory symptoms are present 2
• The risk of morbidity and mortality increases considerably when ANC falls below 200 cells/µL 3

Empiric Antibiotic Therapy (If Febrile)

• Start broad-spectrum antibiotics immediately for any fever (≥38.0°C) - delaying antibiotics increases mortality 1, 2
• Initial regimen should provide coverage against gram-negative organisms and common pathogens 1
• Continue antibiotics until patient has been afebrile for 48 hours AND ANC ≥500 cells/µL, or for 5-7 days if afebrile but ANC remains <500 cells/µL 1
• For high-risk patients (acute leukemia, post-high-dose chemotherapy), antibiotics are often continued for up to 10 days or until ANC ≥500 cells/µL 1

Granulocyte Colony-Stimulating Factor (G-CSF)

• Initiate filgrastim 5 μg/kg/day subcutaneously starting immediately (or the day after TIL infusion in cellular therapy patients) 1, 4
• Continue G-CSF until ANC is at least 500 cells/µL 1
• G-CSF is strongly recommended to reduce incidence of infections, shorten duration of neutropenia, and potentially decrease hospitalization length 1
• For patients on myelosuppressive chemotherapy with high-risk regimens (>50% expected neutropenia rate), primary G-CSF prophylaxis should be used 5

Antimicrobial Prophylaxis

Antibacterial Prophylaxis

• Start levofloxacin or ciprofloxacin 500 mg orally daily with onset of neutropenia 1
• Continue until ANC >500 cells/µL 1

Antifungal Prophylaxis

• Initiate fluconazole 400 mg orally daily (or equivalent) 1
• Continue until ANC >1000 cells/µL 1

Pneumocystis Prophylaxis

• Start trimethoprim-sulfamethoxazole orally three times per week (or alternative) 1
• Continue for 6 months (minimum 3 months) post-treatment and/or until CD4 counts >200 cells/mm³ 1
• Can stop earlier if absolute lymphocyte count normalizes 1

Antiviral Prophylaxis

• Begin acyclovir 400 mg or valacyclovir 500 mg orally twice daily 1
• Continue for 6 months (minimum 3 months) post-treatment and/or until CD4 counts >200 cells/mm³ 1

Supportive Care and Monitoring

• Perform daily complete blood counts to guide transfusion needs and monitor recovery 1
• Transfuse irradiated blood products only: maintain hemoglobin ≥7.0 g/dL and platelets >30,000/mm³ (unless on anticoagulants) 1
• Monitor renal function daily until patient is afebrile and ANC ≥500 cells/µL 1

Neutropenic Precautions

• Avoid crowds, sick contacts, fresh flowers, and raw foods 2
• Practice meticulous hand hygiene 2
• Avoid rectal temperatures, suppositories, and invasive procedures when possible 2

Management of Persistent Fever

At 48 Hours

• If clinically stable: continue initial antibacterial therapy 1
• If clinically unstable: rotate antibacterial therapy or broaden coverage, and seek infectious disease consultation immediately 1

At 4-6 Days

• If pyrexia persists beyond 4-6 days, initiate empiric antifungal therapy 1
• Consider CT scanning and bronchoalveolar lavage if lung infiltrates develop 1

High-Risk Features Requiring Intensive Monitoring

Patients with the following characteristics require closer surveillance 2:

• Expected neutropenia duration >7 days
• Acute leukemia or post-high-dose chemotherapy
• Age >65 years
• Poor performance status
• Presence of comorbidities

Critical Pitfalls to Avoid

• Never delay antibiotics in febrile neutropenia - empiric therapy must start immediately 2
• Do not discontinue antibiotics prematurely if ANC remains <500 cells/µL, even if afebrile 1
• Avoid inadequate follow-up - severe neutropenia requires close monitoring until resolution 2
• Do not initiate or continue chemotherapy or cellular therapy in patients with neutropenic sepsis 1