Chronic neutropenia

What are the symptoms of chronic neutropenia?

Symptoms associated with chronic neutropenia include recurring fevers, mouth sores (ulcers), inflammation of the tissues that surround and support the teeth (periodontitis), and inflammation of the sinuses (sinusitis), throat (pharyngitis), skin (dermatitis), and/or inner ear (otitis). Due to low levels of neutrophils, people with neutropenia may be more likely to get recurring bacterial infections that, in some people, result in life-threatening complications like sepsis. A characteristic feature of chronic neutropenia, especially if it is severe, is a lack or decrease of pus at the site of infections. 

Chronic neutropenia looks very different depending on how low a person’s neutrophil level is in the blood. The risk of infection due to neutropenia correlates with both its severity and duration. 

Those with chronic neutropenia are also at risk of eventually developing bone marrow or blood cancers like myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).

How is chronic neutropenia diagnosed?

Chronic neutropenia can be diagnosed through a complete blood count (CBC) with differential, but a single low neutrophil count is not enough, neutrophil counts must be consistently low for more than three months. In patients with possible cyclic neutropenia, blood counts 2-3 times per week for 4-6 weeks may be necessary. 

While CBC with differential can diagnose chronic neutropenia, CBC with differential cannot determine its cause. Diagnosing the cause of chronic neutropenia starts with a clinical history and hematology evaluation, which may include a bone marrow aspiration. 

Genetic testing is recommended for people with chronic neutropenia. Genetic testing for neutropenia may bring you one step closer to an accurate diagnosis and appropriate clinical management, help you make informed choices about your healthcare, learn the risk for your family members, find resources for your condition, and better understand your options for participating in clinical trial research on investigational therapies. According to a 2022 publication from the International Union of Immunological Societies Expert Committee, variants in more than 20 different genes can cause chronic neutropenia.

Speak with your doctor or contact a genetic counselor through the patient-initiated testing program about getting a no-cost genetic test from the PATH4WARD program, a partnership between X4 Pharmaceuticals and Invitae.

Here are some questions to ask your doctor to see if you may benefit from genetic testing:

• Have I had a genetic test?
• If I had genetic testing done before, should I have it done again since there are now tests that look at more genes?
• There are free genetic tests available with a doctor’s referral or through a patient-initiated testing program. Do I qualify for one?
• Is there a chance my diagnosis might change depending on the results of a genetic test?
• Would my treatment change if a genetic test finds that I have a specific genetic variant causing chronic neutropenia?
• Are there any clinical trials that I might qualify for based on the results of a genetic test?

How is chronic neutropenia treated?

Therapy for chronic neutropenia focuses on preventing infection using specific bacterial or fungal antimicrobials. In case of an infection, your healthcare provider will carefully evaluate the pathogen causing it to determine the appropriate antibacterial or antifungal therapy. 

Another treatment for chronic neutropenia is granulocyte-colony stimulating factors (G-CSF). G-CSF is a man-made version of a hormone that causes bone marrow to make and release neutrophils, which improves a person’s ability to fight off bacterial and fungal infections. G-CSF is administered through an injection, and side effects can include bone pain and headaches. For people with congenital neutropenia, long-term use of G-CSF may cause pre-leukemia or leukemia. In some circumstances, hematopoietic stem cell transplant (HSCT) may be considered depending on the genetic variant and an individual’s response to G-CSF. 

Mavorixafor is an investigational medication that is being studied to see if it can help people with neutropenia by releasing neutrophils from the bone marrow. It works by blocking a receptor known as CXCR4 that is present on the surface of immune cells. Mavorixafor has been studied in healthy volunteers as well as people with WHIM syndrome (another PI) and cancer, and all studies showed increases in neutrophil count.