From the Guidelines
Yes, it is possible to have a genetically low white blood cell (WBC) and neutrophil count, as seen in conditions such as severe chronic neutropenia, which can be congenital, cyclic, or idiopathic 1.
Key Points to Consider
- These conditions can be effectively managed with granulocyte-colony stimulating factor (G-CSF) therapy, which helps normalize neutrophil counts and prevent infections 1.
- The dosage of G-CSF varies depending on the type of neutropenia, with congenital neutropenia requiring higher doses (3-10 mcg/kg/d) compared to idiopathic and cyclic neutropenia (1-3 mcg/kg/d) 1.
- It is essential to diagnose and monitor these conditions carefully, as patients with severe congenital neutropenia are at risk of developing myelodysplasia and leukemia, regardless of G-CSF treatment 1.
- Benign ethnic neutropenia, also known as constitutional neutropenia, is another condition where individuals have a lower baseline neutrophil count without increased susceptibility to infections, often found in people of African, Middle Eastern, or West Indian descent.
- In such cases, no treatment is needed, but establishing a normal baseline is crucial to avoid unnecessary medical interventions.
Important Considerations
- The genetic basis of these conditions, such as variations in the Duffy Antigen Receptor for Chemokines (DARC) gene, now called ACKR1, plays a significant role in understanding the underlying mechanisms 1.
- Despite the lower WBC and neutrophil counts, immune function remains intact in individuals with benign ethnic neutropenia, as their neutrophils function normally, and the body can still increase production during infections.
From the Research
Genetically Low WBC and Neutrophil Count
- It is possible to have a genetically low White Blood Cell (WBC) and neutrophil count, as seen in severe congenital neutropenia (SCN) 2, 3, 4.
- SCN is caused by germline mutations, most commonly in the ELANE gene, which impacts neutrophil maturation and leads to a high risk of life-threatening infections 2, 3, 4.
- Patients with SCN often have an absolute neutrophil count (ANC) below 0.5 x 10(9)/L and are at increased risk of developing myelodysplastic syndrome or leukemia (MDS/L) 3, 4.
- Treatment options for SCN include granulocyte colony-stimulating factor (G-CSF) therapy, which can increase the ANC in most patients, and hematopoietic stem cell transplantation (HSCT) for those who are refractory to G-CSF or have developed MDS/L 2, 3, 4.
Causes of Low WBC and Neutrophil Count
- Congenital neutropenia can be caused by mutations in genes such as ELANE, HAX1, and SBDS 5.
- Acquired neutropenia can be caused by chemotherapy, infections, autoimmune diseases, or nutritional deficiencies 5.
- Diagnostic evaluation of neutropenia requires a stepwise approach incorporating clinical history, blood counts, peripheral smear, bone marrow biopsy, and molecular or serologic testing 5.
Treatment Options
- Treatment of neutropenia depends on the etiology and severity and includes G-CSF, immunosuppressants, antimicrobial prophylaxis, and HSCT in selected cases 2, 3, 5.
- G-CSF therapy is effective in increasing the ANC in most patients with SCN, but some patients may be refractory to treatment or develop adverse events such as malignant transformation 4.
- HSCT is the only curative treatment for SCN and can provide excellent outcomes with minimal toxicity when using reduced intensity conditioning regimens 2, 3.