From the Guidelines
Chronic leukopenia can be caused by various conditions, including hematologic malignancies, such as chronic and acute leukemias, non-Hodgkin’s lymphoma, and myelodysplastic syndromes, which can lead to leukopenia due to infiltration of the marrow with malignant cells or a dysfunctional marrow 1.
Causes of Chronic Leukopenia
- Hematologic malignancies, such as chronic and acute leukemias, non-Hodgkin’s lymphoma, and myelodysplastic syndromes, can cause chronic leukopenia due to infiltration of the marrow with malignant cells or a dysfunctional marrow 1.
- Certain malignancies, like chronic lymphocytic leukemia (CLL), can lead to hypogammaglobulinemia, increasing susceptibility to infections, particularly those caused by encapsulated bacteria like Streptococcus pneumoniae 1.
- Advanced or refractory malignancy can increase the risk of infectious complications due to marrow failure from the underlying disease itself and from multiple lines of prior cytotoxic or immunosuppressive therapy 1.
- Refractory hematologic malignancies, such as fludarabine-refractory CLL, can significantly increase the risk of developing severe infections, including bacterial, viral, fungal, and opportunistic pathogens 1.
Clinical Considerations
- Patients with chronic leukopenia are at increased risk of infections, particularly those with advanced or refractory malignancy, and require close monitoring and management to prevent and treat infectious complications 1.
- The underlying cause of chronic leukopenia should be identified and treated, which may involve medication adjustments, nutritional supplementation, or specific treatments for bone marrow disorders.
- A comprehensive approach to managing chronic leukopenia should include consideration of the patient's overall health status, including nutritional status, performance status, and presence of other comorbidities.
From the FDA Drug Label
Mild, moderate, or severe leukopenia, agranulocytosis, granulocytopenia, WBC decreased
- Clozapine can cause chronic leukopenia.
- The mechanism by which clozapine causes neutropenia (which can be associated with leukopenia) is unknown and is not dose-dependent.
- Risk of neutropenia appears greatest during the first 18 weeks on treatment and then declines 2.
- Concomitant use of clozapine with other drugs that affect the cytochrome P450 isozymes (e.g., CYP1A2, CYP3A4, and CYP2D6) can increase the risk of adverse reactions, including leukopenia 2.
From the Research
Causes of Chronic Leukopenia
- Chronic leukopenia can be caused by various factors, including:
- Intrinsic causes such as impaired proliferation and maturation of myeloid progenitor cells in the bone marrow 3
- Extrinsic causes, which can be varied 3
- Autoimmune disorders, such as autoimmune neutropenia (AIN) 4
- Systemic lupus erythematosus, which can cause bone marrow involvement and lead to aplastic anemia 5
- Certain medications, such as clozapine, which can cause hematologic abnormalities, including anemia and agranulocytosis 6, 7
- Chronic leukopenia can also be a complication of chronic lymphocytic leukemia (CLL), resulting in autoimmune cytopenias, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia (PRCA), or autoimmune neutropenia (AIN) 4
- The pathogenesis of hematologic abnormalities due to certain medications, such as clozapine, is not fully understood, but suggested mechanisms include a direct toxic effect on the erythroid precursor cells or formation of a drug-antibody complex 7