What is the management approach for a patient with a low-grade fever following a stem cell infusion, with otherwise stable hemodynamics?

Management of Low-Grade Fever Following Stem Cell Infusion

Immediate Assessment and Supportive Care

This fever is most likely a benign transfusion-related reaction rather than infection, and the patient should receive symptomatic treatment with acetaminophen while being monitored closely for signs of infection or cytokine release syndrome (CRS). 1

Initial Evaluation Within 30 Minutes

• Perform focused physical examination looking specifically for: hemodynamic instability (hypotension, tachycardia), respiratory compromise (hypoxia, increased work of breathing), signs of infusion reaction (rash, urticaria, chest pain, back pain), and catheter site infection 1

• Obtain vital signs every 15-30 minutes for the first 2 hours, including temperature, blood pressure, heart rate, respiratory rate, and oxygen saturation 1

• Draw blood cultures (two sets) and obtain urinalysis with culture if the patient has an indwelling catheter, even though infection is unlikely at this early timepoint 1

• Check complete blood count, chemistry panel, and inflammatory markers (C-reactive protein, ferritin) to establish baseline and assess for early CRS 1

Distinguishing Transfusion Fever from Infection

Fever occurring within 30 minutes to 24 hours post-infusion is typically transfusion-related rather than infectious. The median time to fever onset in transfusion reactions is 2.5 hours (range 0-18 hours), with peak temperature occurring at median 7.8 hours post-infusion 2. In one study, 82.5% of haploidentical transplant recipients developed fever after stem cell infusion, with none attributed to infection 3.

• Transfusion-related fever characteristics: Temperature 38.0-40.5°C, onset within 24 hours of infusion, absence of hemodynamic compromise, resolution within 96 hours without antibiotics 3, 2

• CRS Grade 1 criteria: Fever ≥38°C without hypotension or hypoxia 1

Antibiotic Decision Algorithm

DO NOT Start Empirical Antibiotics If:

• Patient is hemodynamically stable (normal blood pressure, no vasopressor requirement) 1
• No hypoxia (oxygen saturation >90% on room air) 1
• Fever occurred within 24 hours of infusion with no other infectious signs 3, 2
• Patient is NOT neutropenic (ANC >500 cells/mm³) 1

START Empirical Broad-Spectrum Antibiotics If:

• Patient is neutropenic (ANC <500 cells/mm³) with fever ≥38.0°C, regardless of timing or suspected etiology 1

• Hemodynamic instability develops (hypotension requiring fluids or vasopressors) 1

• Hypoxia develops (oxygen saturation <90% on room air or requiring supplemental oxygen) 1

• Fever persists beyond 48-72 hours without alternative explanation 1

• New infectious signs emerge (productive cough, dysuria, cellulitis, diarrhea) 1

If antibiotics are indicated, administer within 30 minutes as rapid administration (<30 min) reduces fever duration compared to delayed administration (median 1.5 vs 6.5 days, p=0.003) 4. Use cefepime 2g IV every 8 hours as monotherapy for empirical coverage 5, or institutional equivalent broad-spectrum regimen 1.

Monitoring Protocol for Stable Patients

First 24 Hours Post-Infusion

• Continue vital signs every 2-4 hours including temperature, blood pressure, heart rate, oxygen saturation 1

• Administer acetaminophen 650-1000mg orally every 6 hours for symptomatic fever control 1

• Maintain adequate hydration with intravenous fluids as clinically indicated 1

• Reassess CRS grading every 12 hours or more frequently if clinical status changes 1

When to Escalate Care

Admit patient for closer monitoring or escalate treatment if:

• Fever persists >48 hours without defervescence 1
• Development of hypotension (systolic BP <90 mmHg or drop >20 mmHg from baseline) 1
• New oxygen requirement or worsening respiratory status 1
• Altered mental status or neurologic symptoms 1
• Signs of organ toxicity (elevated creatinine, liver enzymes, coagulopathy) 1

Critical Pitfalls to Avoid

• Do not reflexively start antibiotics for isolated fever within 24 hours of stem cell infusion in non-neutropenic, hemodynamically stable patients, as this represents transfusion-related fever in the majority of cases 3, 2

• Do not use corticosteroids for fever management in the immediate post-infusion period, as they are lymphocytotoxic and may impair stem cell engraftment 1

• Do not delay antibiotic administration if the patient IS neutropenic, even if transfusion-related fever is suspected, as neutropenic fever requires empirical coverage within 30-60 minutes 1, 4

• Do not assume fever resolution means no infection - continue monitoring for 48-72 hours as bacterial infections can declare themselves later 1

• Do not overlook early CRS, which presents initially as isolated fever but can rapidly progress to hypotension and hypoxia requiring tocilizumab and steroids 1