From the Guidelines
Neutropenia in adults should be managed with immediate empiric broad-spectrum antibiotics in cases of febrile neutropenia, and granulocyte colony-stimulating factors (G-CSF) may be administered to stimulate neutrophil production in patients with prolonged neutropenia, as recommended by the most recent guidelines 1.
Definition and Causes of Neutropenia
Neutropenia in adults is defined as an absolute neutrophil count (ANC) below 1,500 cells/μL, with severe neutropenia being less than 500 cells/μL. The underlying cause of neutropenia may include medications, infections, autoimmune disorders, nutritional deficiencies, or hematologic malignancies.
Management of Neutropenia
When managing neutropenia, the first step is to identify the underlying cause. For drug-induced neutropenia, discontinuing the offending medication is essential. In cases of severe neutropenia with fever (febrile neutropenia), immediate empiric broad-spectrum antibiotics are necessary, typically with an antipseudomonal beta-lactam like piperacillin-tazobactam (4.5g IV every 6 hours) or cefepime (2g IV every 8 hours) 1.
Use of G-CSF
For patients with prolonged neutropenia, G-CSF such as filgrastim (5-10 μg/kg/day subcutaneously) may be administered to stimulate neutrophil production, as supported by guidelines from the American Society of Clinical Oncology 1.
Preventive Measures
Preventive measures include good hygiene, avoiding raw foods, and limiting exposure to potential infections. Regular monitoring of complete blood counts is crucial for patients at risk. The severity of neutropenia directly correlates with infection risk because neutrophils are the primary cellular defense against bacterial and fungal infections, making prompt recognition and management essential to prevent life-threatening complications 1.
Key Considerations
- The risk of infection increases with the depth and duration of neutropenia, with the greatest risk occurring in patients who experience profound, prolonged neutropenia after chemotherapy 1.
- Prevention and appropriate management of febrile neutropenia is important because the rate of major complications is approximately 25% to 30% and mortality up to 11% 1.
- The use of antimicrobial prophylaxis should be considered in adult patients with cancer-related immunosuppression, as recommended by the ASCO and IDSA clinical practice guideline update 1.
From the FDA Drug Label
The safety and efficacy of filgrastim to reduce the incidence and duration of sequelae of neutropenia (that is fever‚ infections, oropharyngeal ulcers) in symptomatic adult and pediatric patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia was established in a randomized controlled trial conducted in patients with severe neutropenia (Study 7).
ANC response from baseline (< 500/mm3) was defined as follows: • Complete response: median ANC > 1,500/mm3 • Partial response: median ANC ≥ 500/mm3 and ≤ 1,500/mm3 with a minimum increase of 100% • No response: median ANC < 500/mm3
There were 112 of 123 patients who demonstrated a complete or partial response to filgrastim treatment
Filgrastim is effective in reducing neutropenia in adults. The study showed that filgrastim treatment resulted in a complete or partial response in 112 out of 123 patients with severe chronic neutropenia, with a significant increase in median ANC.
- Key findings:
- Complete response: median ANC > 1,500/mm3
- Partial response: median ANC ≥ 500/mm3 and ≤ 1,500/mm3 with a minimum increase of 100%
- No response: median ANC < 500/mm3
- Main efficacy endpoint: ANC response from baseline (< 500/mm3) 2
From the Research
Definition and Diagnosis of Neutropenia
- Neutropenia is defined as an absolute neutrophil count (ANC) less than 1.5 × 10(9)/L 3, 4, 5
- Severe neutropenia is defined as an ANC less than 0.5 × 10(9)/L 3
- Diagnosis of neutropenia involves laboratory evaluation, including repeat complete blood cell counts (CBCs) with differentials and bone marrow examination with cytogenetics 4
Causes and Consequences of Neutropenia
- Neutropenia can be caused by genetic variations, autoimmune disorders, HIV, hepatitis, and other underlying conditions 4, 5
- Severe chronic neutropenia can lead to an increased risk of bacterial and fungal infections, and may also increase the risk of developing myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) 4
Treatment of Neutropenia
- Treatment of severe chronic neutropenia includes administration of granulocyte colony-stimulating factor (G-CSF) 3, 4, 6
- Patients with acute febrile neutropenia should be treated with antibiotics, and those at high risk of severe neutropenia should be treated prophylactically with G-CSF 3
- Hematopoietic stem cell transplantation is a curative therapy for congenital neutropenia with MDS/AML or with cytogenetic abnormalities indicating impending conversion 4