In patients with severe chronic neutropenia (SCN), treatment with granulocyte colony-stimulating factor (G-CSF) appeared to show long-term benefits. This is according to results of an analysis recently published in the journal Blood Advances.

SCN is associated with a blood neutrophil count of <0.5×109/L for more than 3 months, the study investigators explained in their report. It is an uncommon condition that often presents with fever and/or a variety of types of bacterial infections. G-CSF was approved by the US Food and Drug Administration for treatment of SCN in 1994, with a requirement for a longitudinal follow-up, including safety data, that resulted in the creation of the Severe Chronic Neutropenia International Registry (SCNIR) that year.

In this prospective, longitudinal analysis, all patients in the United States included in the SCNIR from May 1994 through June 2020 were evaluated for long-term outcomes. Included patients had absolute neutrophil counts of <0.5×109/L on 3 or more occasions over 3 or more months. Patients were grouped for analyses by categories of SCN, including cyclic neutropenia, congenital neutropenia, and autoimmune/idiopathic neutropenia.


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The mean follow-up time was 9.3 years. A total of 1752 patients were evaluable, with over 16,000 patient-years of observational data available for analysis.

Among patterns the researchers found in clinical histories, cyclic and congenital neutropenia symptoms were often present not long after birth. However, patients experienced delays in diagnoses often attributed to a difficulty in distinguishing between acute febrile episodes with the condition and the infections generally occurring in children of the age group.

Genetic testing also revealed geographic patterns of mutations in evaluated genes; mutations in the ELANE gene were considered the main cause of cyclic and congenital neutropenia. Other mutations, such as in JAGN1 and HAX1 genes, were more common in European and Middle Eastern patients than in those of the United States. Patterns of absolute neutrophil counts or absolute lymphocyte counts also appeared to differ by category of neutropenia, with congenital neutropenia showing the lowest neutrophil counts prior to G-CSF treatment (P =.006).

G-CSF had been given to most patients and for long periods of time. Median neutrophil counts were higher in patients after treatment with G-CSF, across age categories and forms of SCN. There also appeared to be less hospital utilization for infections and less mortality related to infections after initiating G-CSF.

Myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) developed in 4.4% of patients overall, and lymphoid malignancies were less common. Patients with congenital neutropenia showed the highest rate of developing MDS/AML, which occurred in 11.3% of patients with this type of neutropenia. No patients with autoimmune/idiopathic neutropenia developed MDS or AML, while 1.5% of patients with this category of neutropenia developed lymphoid malignancies.

As a preventive agent in patients with SCN, the researchers found that G-CSF was associated with fewer cases of febrile neutropenia, infections, and antibiotic use. “The clinical benefit is enormous: because of fewer febrile episodes, G-CSF promotes well-being and increases productivity at work and in school,” the study investigators wrote in their report.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Dale DC, Bolyard AA, Shannon IV JA, et al. Outcomes for patients with severe chronic neutropenia treated with granulocyte colony-stimulating factor. Blood Adv. 2022;6(13):3861-3869. doi:10.1182/bloodadvances.2021005684