Infections: risk in oncohaematological children. What is Neutropenia?

By Cristiano Antonino On May 18, 2023

Oncohaematological children and infections: in paediatric patients with oncohaematological diseases the immune defences are impaired, thus increasing the risk of infections

Children and young people with oncohaematological disease often have a reduced immune system function

Because of this fragility, they are at greater risk of contracting an infection.

This immunological deficit condition is brought about by the disease itself as well as by the chemo-immune-radiotherapy treatments used for treatment.

In this type of patient, infections are a potentially lethal danger and it is therefore necessary to try to prevent them as best as possible.

White blood cells are the body’s first line of defence against bacteria, viruses and fungi. There are several subtypes, of which neutrophils and lymphocytes are undoubtedly the most important.

Lymphocytes are mainly responsible for the defence against viruses and fungi.

If their number is reduced (lymphopenia), the risk of viral and fungal infection or reactivation increases, such as by:

Influenza-type respiratory viruses;
Cytomegalovirus (CMV);
Epstein-Barr virus (EBV);
Herpes virus type 6 (HHV6).

The risk is significantly higher in patients with haematological disease or undergoing a bone marrow transplant.

Neutrophils, on the other hand, are white blood cells that are particularly active against bacterial infections.

Their reduction to values below 500 cells/µL (neutropenia) exposes them to an infectious risk, which may manifest itself in clinical pictures ranging from mild to very severe (septic shock).

Fungal infections (typically Candida and Aspergillus), on the other hand, are more frequently seen in subjects who experience prolonged periods of lymphopenia and neutropenia.

It should be emphasised, however, that in most cases of febrile neutropenia it is not possible to isolate the responsible germ.

The onset of fever during neutropenia is a very common occurrence, occurring in about one third of patients.

Fever is defined as:

The single occurrence of an axillary temperature greater than or equal to 38.3°C;
A temperature greater than or equal to 38°C that lasts for more than one hour or is detected at least twice within a 12-hour period.

This condition is considered a real medical emergency in oncohaematological children and young people because it must be considered, until proven otherwise, a sign of an infection.

Given the reduced reactivity of the immune system, other typical symptoms of infection may be absent and fever may be the only alarm bell.

Moreover, due to the lack of effective defence mechanisms, germs that are considered harmless/unaggressive in immunocompetent individuals in the neutropenic patient can lead to even severe infections.

There are other factors that contribute to increased susceptibility to infection in oncohaematology patients, the most important of which are disruption of skin and mucosal barriers (oral, gastrointestinal, etc.) and gastrointestinal microbial translocation.

The disruption of natural barriers, such as skin and mucous membranes, damaged and made fragile by chemo- or radiotherapy treatments, tumour infiltration or surgery, creates a potential gateway for pathogenic microorganisms.

Invasive procedures required for diagnostic and therapeutic purposes (insertion of central venous catheters or needle cannulae, bone marrow aspirates, lumbar punctures, biopsies, etc.) can also encourage germs to enter the body.

An additional risk factor to be considered is malnutrition: attempting to maintain an adequate nutritional status in patients undergoing cancer treatment should be considered a priority objective for a good outcome.

In the event of fever occurrence, especially during neutropenia, it is always advisable to contact the oncohaematologist, especially if the temperature rise is associated with one of the following symptoms

Excessive tiredness or weakness;
Muscle pain;
Cough and/or difficulty breathing;
Warm redness or swelling (swelling) of the skin;
Abdominal pain, diarrhoea, vomiting;
Aphthae and ulceration of the oral cavity (mucositis);
Confusion or disorientation.

The doctor will agree on the urgency with which the patient should be taken to hospital for examination.

At the same time as the clinical evaluation, the following will generally be performed in the oncohaematological children

Control haematochemical tests;
Microbiological tests on blood (taken from central venous catheter and peripheral vein) and on any other material taken from the site where the infection is suspected (urine, faeces, CSF, sputum or phlegm, secretions from skin lesions, etc.);
Chest X-ray, particularly if respiratory symptoms are present. In selected cases, a Computed Tomography (CT) scan of the chest is also performed;
Abdominal echography, if gastrointestinal symptoms are also present;
Echocardiogram, if signs of haemodynamic instability are present or if central venous catheter infection is suspected.

Treatment of fever during neutropenia is based on the assumption that it is a sign of an ongoing infection

Since it is not immediately and not always possible to isolate the causative organism, treatment involves the use of broad-spectrum anti-infective drugs administered intravenously in order to act on the widest possible range of infectious agents.

Treatment is usually continued until neutrophil values rise again and until at least 24 hours after the fever has disappeared.

Therapy can be rescheduled at a later date and microbiological tests can be used to isolate a specific germ or when fever persists despite the treatment set.

If, on the other hand, fever is not associated with clinical warning symptoms or the patient is not neutropenic, the therapeutic approach may be less ‘aggressive’ and be based on oral therapy and careful observation at home.

There are currently no studies that have demonstrated the effectiveness of preventive antibiotic therapies in oncohaematological patients, with the exception of prophylaxis with sulfamethoxazole+trimethoprim (BACTRIM®).

The latter prevents opportunistic pulmonary infection by Pneumocystis jirovecii and is indicated for the duration of chemo- or radiotherapy treatment.

Antifungal prophylaxis, on the other hand, is proven effective for patients who, as mentioned, experience prolonged periods of lymph/neutropenia.

In the course of neutropenia, granulocyte growth factor (G-CSF), a drug that does not reduce the incidence of infectious complications, but promotes a more rapid rise in neutrophil values, may be associated.

This drug can be administered intravenously or subcutaneously via a device that can also be used independently at home.

The most effective measures to prevent infection remain those related to careful hygiene of the patient, carers and the environment.

Such measures include:

Frequent hand washing (with sanitising gels or, if visibly soiled, with soap and water for at least 15 seconds
Careful, daily personal and oral hygiene;
The avoidance of crowded and enclosed places;
Avoidance of direct contact with people with cold or flu symptoms;
The avoidance of raw, unpasteurised, not thoroughly washed and peeled or inadequately preserved food;
The avoidance of close and continuous contact with animals, domestic or otherwise;
The weekly dressing of the central venous catheter insertion point (performed in sterility by experienced nursing staff);
The postponement of any elective dental procedures;
The vaccination of persons living in close contact with the patient (especially anti-flu and anti-COVID).

Infectious complications in children and young people with neoplasia are undoubtedly one of the most frequent and worrying variables in paediatric oncohaematology.

The availability of increasingly effective anti-infectious drugs and the possibility of carrying out a targeted and early diagnosis guarantee, in most cases, the implementation of an effective and decisive therapy, allowing the treatments necessary for the treatment of the underlying disease to be continued on time.

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