Leukopenia?

From the Guidelines

Leukopenia is a condition characterized by low white blood cell count, which can be managed by holding or reducing the dose of the offending medication, such as dasatinib, until the white blood cell count recovers to a safe level, typically ANC ≥ 1000/mm3 1.

Management of Leukopenia

• In cases of Grade 3-4 neutropenia (ANC < 500/mm3), the medication should be held until ANC ≥ 1000/mm3, and then resumed at the original starting dose if recovery occurs within 7 days, or reduced one dose level if ANC < 500/mm3 for more than 7 days 1.
• Growth factors, such as granulocyte-colony stimulating factor (G-CSF), can be used in combination with dasatinib for patients with resistant neutropenia and thrombocytopenia 1.
• Patients with leukopenia due to disease-related cytopenias may require dose escalation of dasatinib to 180 mg daily, while those with treatment-related cytopenias may require dose reduction or discontinuation of the offending agent 1.
• In severe cases of leukopenia, patients may require hospitalization and broad-spectrum antibiotic therapy to prevent or treat infections.
• It is essential to monitor the patient's white blood cell count closely and adjust the treatment plan accordingly to minimize the risk of infections and other complications associated with leukopenia 1.

From the FDA Drug Label

To improve and standardize understanding, “severe neutropenia” replaces the previous terms severe leukopenia, severe granulocytopenia, or agranulocytosis Severe neutropenia, ANC less than (<) 500/μL, occurs in a small percentage of patients taking clozapine and is associated with an increase in the risk of serious and potentially fatal infections.

Leukopenia is mentioned in the context of severe leukopenia being replaced by the term severe neutropenia.

• The drug label does not provide a direct answer to the question of leukopenia, but it does discuss neutropenia, which is a type of leukopenia.
• The label states that severe neutropenia (ANC less than 500/μL) occurs in a small percentage of patients taking clozapine and is associated with an increased risk of serious and potentially fatal infections 2.
• However, the label does not provide specific information on the incidence or management of leukopenia itself.

From the Research

Definition and Causes of Leukopenia

• Leukopenia is an abnormal reduction of circulating white blood cells, especially the granulocytes 3
• It may result from reduced production of white blood cells or increased utilization and destruction, or both 3
• Infection, drugs, malignancy, megaloblastosis, hypersplenism, and immunoneutropenia are responsible for most cases of neutropenia 3

Management and Treatment of Leukopenia

• Granulocyte colony-stimulating factor (G-CSF) has been used to accelerate white blood cell (WBC) count recovery in patients with leukopenia 4, 5
• G-CSF treatment can be effective in achieving WBC count recovery in addition to changes in immunosuppression and prophylaxis medications 4
• The major danger of neutropenia is the risk of infection, and management requires identification of the cause and effective antimicrobial therapy 3

Use of G-CSF in Specific Patient Populations

• G-CSF has been used in kidney and liver transplant recipients with leukopenia, and has been shown to be safe and effective in this population 5
• G-CSF has also been used in patients with solid tumors and chemotherapy-induced leukopenia, and has been shown to be effective in reducing the duration of leukopenia 6
• In patients with HIV-associated Kaposi sarcoma, G-CSF has been used to treat virus and drug-induced leukopenia, and has been shown to be effective in stimulating white blood cell production 7

Predictors of Response to G-CSF

• Undergoing four or more chemotherapy courses and heart failure have been identified as independent risk factors for poor response to G-CSF 6
• Previous radiotherapy, number of chemotherapy courses, high G-CSF dosage, and hypoalbuminemia have also been associated with poor G-CSF response 6