the Management of Neutropenia in Pediatric Age Groups

Neutropenia is defined as a reduction in the absolute neutrophil count (ANC) below the lower limit of the normal range for the age and ethnic origin of the affected subject. In pediatrics, it is important to note that normal values for the ANC vary by age. The lower normal limit in the 1^st week of life is 5000/mm₃, and this value decreases to 1000/mm³ between the 2^nd week of life and 1 year of age. After the age of 1 year, an ANC below 1500/mm³ is defined as neutropenia, between 1000 and 1500/mm³ as mild, between 500 and 1000/mm³ as moderate, and below 500/mm³ as severe neutropenia ¹. Certain populations (e.g., African-Americans, Yemenite Jews, and certain Arabs) normally have slightly lower white blood cell count and ANC values ². Neutropenia is a decrease in circulating (i.e., nonmarginal) neutrophils in the blood ¹. The nonmarginal pool constitutes only 4-5% of total body neutrophil stores; while most of the neutrophils in the body are contained in the bone marrow, either as mitotically active (one-third) or postmitotic mature cells (two-thirds) ².

Neutropenia can be classified as congenital or acquired. Congenital neutropenia is a heterogeneous hereditary group of disorders that are characterized by intermittent episodes, or continuous severe or moderate neutropenia persisting for at least 3 months and can develop at any stage of the proliferation and maturation phases of neutrophils, secondary to genetic causes. Although it occurs only rarely, congenital neutropenia is a significant condition that causes recurrent infections and has a chronic course^3,4. Acquired neutropenia is more common than congenital neutropenia, with the most common causes being infections, drugs, and chronic benign neutropenia in infancy and childhood. It is believed that the majority of cases defined as chronic benign neutropenia in infancy and childhood represent an autoimmune neutropenia that is parallel to childhood idiopathic thrombocytopenic purpura ⁴. Apart from these, bone marrow involvement, nutritional causes, immunological disorders, metabolic disorders, autoimmune lymphoproliferative syndrome, and Evans syndrome are other causes of acquired neutropenia ^3,4.

Neutropenic individuals are at increased risk of infection. The greatest susceptibility of infection is seen with ANC below 500 neutrophils/mm³, and when neutrophil production remains low without recovery. Gram-negative bacteria, viruses, fungi, and opportunistic pathogens are also common. The cornerstone for evaluating a patient with neutropenia is a thorough history and physical exam in addition to laboratory data ⁵. In recent years, advances in genomics have identified novel genes implicated in the pathogenesis and/or evolution of neutropenia, unraveled the underlying pathogenic mechanisms, and opened the way for novel tailored therapies ^1-4,6,7. A number of comprehensive reviews have been produced by experts in the field aiming to disseminate the knowledge and guide clinicians for the accurate diagnosis, follow-up, and treatment of neutropenia patients, particularly those with chronic disease ^1-4,6-11. Real world data, however, arising from a survey within the Cooperation in Science and Technology European Network for the Innovative Diagnosis and Treatment of Chronic Neutropenias (EuNet-INNOCHRON; https://eunet-innochron.eu/) involving physicians with special interest in neutropenias have shown that the work-up of patients with chronic neutropenia is mostly based on the physicians’ experience and local practices rather than on the guided clinical and laboratory evidence ¹². Thus, the diagnosis and monitoring of neutropenic patients remains varied and challenging. Overall, continuous education of hematologists on known and arising neutropenia entities and guided diagnostic, follow-up, and treatment strategies are particularly important.

➡️Purpose and Scope

These guidelines have been developed to standardize the delivery of services and to implement the guidance on the prevention, diagnosis and management of neutropenia in pediatric age groups. It provides guidance to primary health care providers, pediatricians and specially trained nurses.

The guidelines aimed to provide an evidence-based document for the

      -    Identification of conditions associated with neutropenia.

      -    Diagnostic approaches in the target population.

      -    Treatment of neutropenia and the associated complications in the target population.

      -    Prevention and monitoring of neutropenia.

This version of the guideline includes recommendations and good practice statements for

·       Diagnosis of neutropenia in pediatric age groups.

·       Management of neutropenia in pediatric age groups.

·       Prevention of neutropenia in pediatric age groups