Benign Ethnic Neutropenia

Africa has a higher cancer mortality rate than other parts of the world. African cancer patients sometimes have delayed, reduced dosages or are denied chemotherapy because most Africans have benign ethnic neutropenia.

What is benign ethnic neutropenia?

Benign ethnic neutropenia (BEN) is a condition without any symptoms and is disproportionately seen in individuals of African, Caribbean, Middle Eastern and West Indian descent. It is characterised by persistent low neutrophil counts or a reduced absolute neutrophil count (ANC) less than 1500/uL.

Neutrophils are the most common type of white blood cell and help your immune system fight infections and heal injuries. Unlike other neutropenia, people with BEN do not have any risk of oral or systemic infections, fever or sepsis.?

BEN is chronic and congenital (present from birth) and is most common in people of African, Middle Eastern and West Indian descent.

As a health practitioner, you cannot diagnose a person with BEN unless the person has been repeatedly tested with a low neutrophil count of less than 1000/uL to 1,500/uL without any secondary cause or symptoms.

Risk factors of benign ethnic neutropenia

The exact prevalence of BEN is unknown, with 25–50% of Africans and 4.5% of African-Americans living in the US having an absolute neutropenia count (ANC) between 1000 and 1500. and are not at any increased risk of infection.

Some studies show that BEN is strongly associated with a genetic change in the Duffy Antigen Receptor for Chemokine (DARC) gene located on chromosomes. This genetic change also protects against malaria, which is very common among African, Caribbean, Middle Eastern and West Indian descent.?

Diagnosis of benign ethnic neutropenia

The diagnosis of BEN is of exclusion. As a health practitioner, you should eliminate all other causes of neutropenia.

Some of these exclusions are:

• A person with BEN should have a laboratory test that shows that the person has an absolute neutrophil count that is less than 1500/uL.
• The person must not have symptoms of any infection.
• The person must not have a medical history or recent examination of another diagnosis.
• The person must not have any other laboratory test that gives another reason for neutropenia.
• The person must repeat the performed laboratory test at least two weeks apart.
• If the person is diagnosed with BEN and has no symptoms such as fever, oral ulcers, an enlarged spleen or swollen lymph nodes, then there is no need for further investigations. But if the person has other symptoms, further physical examinations are needed to find another cause of the neutropenia.

Symptoms of benign ethnic neutropenia

Although neutropenia has many symptoms, including recurrent infections, anaemia, thrombocytopenia, splenomegaly or lymphadenopathy, BEN has no apparent symptoms.?

However, some of its significant features are:

• Persistent absolute neutrophil count of less than 1500/uL, usually between 1000/uL and 1500/uL
• No increased risk of infections
• Absence of secondary causes of neutropenia
• Absence of other cytopenias
• Absence of splenomegaly
• Absence of lymphadenopathy

How does benign ethnic neutropenia affect cancer treatment?

As a health practitioner, if your BEN-free patient has cancer, you know that fighting cancer alone isn't enough for them to live; they need to manage the side effects of the disease and its treatments, some of which may lead to other conditions or illnesses.

One common significant side effect of cancer or cancer treatment is that your patient has to watch out for their neutropenia because chemotherapy reduces the number of neutrophils in the human body.

It is much riskier for Africans with low neutrophils due to BEN before cancer treatment. This lower baseline absolute neutrophil counts in Africans can lead to more frequent dose reductions, discontinuations in chemotherapy treatments, and thus, lower survival rates and an increase in mortality rate.

These dose reductions and discontinuations in treatment are because chemotherapy guidelines clearly state that "no person should be treated with chemotherapy if the neutrophils are below a predefined level."

The predefined level for neutrophils is above 2000/uL, which means these guidelines do not consider an individual patient with hidden neutropenia with no symptoms or infections.

Without this consideration, Africans with cancer would not be open to chemotherapy. It might be because scientists who created these guidelines thought that people with BEN become more vulnerable to infections and illnesses.

According to a study, although Africans with BEN have lower absolute neutrophil counts before and after chemotherapy, the percentage decline in absolute neutrophil counts after receiving chemotherapy was similar in other descents that do not have benign ethnic neutropenia (i.e. Americans).

The study also shows that the total duration of cancer treatment in people with BEN was four weeks more than in those that didn't have neutropenia. It is due to the more frequent dose reductions and holding chemotherapy due to lower baseline absolute neutrophil counts.

There is also evidence that cancer patients with BEN are not at an increased risk of developing neutropenic fever after the introduction of chemotherapy when compared with other cancer patients, although another study said otherwise.

All these studies further suggest that health practitioners should carefully consider cancer patients with BEN, and they should have different neutrophil count thresholds for holding and discontinuing chemotherapy.?

Although further studies may be able to show that lower absolute neutrophil count parameters are appropriate in this unique subgroup of patients, patients with BEN may be excluded from chemotherapy clinical trials and safely receive chemotherapy if their absolute neutrophil count (ANC) is between 500/uL and 1500/uL due to their no symptoms (and no infections) neutropenia.

As a health practitioner, your cancer patients with BEN can undergo chemotherapy. There's no need to discontinue the process or put it on hold. If you must reduce their dosage, you have to increase the duration of their treatment accordingly, so they would have the exact dosage as other cancer patients that do not have BEN but within a more extended period.

Could denial of chemotherapy because of BEN contribute to the lower survival rates from breast cancer in black and ethnic minorities despite breast cancer rates being the same across all ethnicities?

There is little research and knowledge about BEN in relation to frontline clinical management with chemotherapy. Clinical management guidance also needs to include managing those presenting with BEN. The automatic clinical response seems to be to delay treatment or to reduce the dosage until the neutrophil level is at 1500/uL, even when there is no evidence of an increased risk of potential adverse effects. Should neutrophil levels needing to be at least 1500u/L be challenged?

There is a need for awareness about BEN and discussions about the clinical management of cancer patients with BEN needing chemotherapy. More inclusive research is also required because, currently, there is very little inclusion of Africans in cancer research.?

I hope I have been able to enlighten you in this edition of The Missing Link and that you can use the information to serve your patients better.

I am Helen Fosam , a medical writer passionate about improving health outcomes through continuing medical education in Africa.

To learn more about our courses and what we do, connect with The MiLHO Initiative and check out our website https://milho.net/ .

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Till next week,

Helen