Infectious Episodes in Paediatric Patients with Moderate-To-Severe Chronic Benign Neutropenia and Normal Bone Marrow Evaluation

Abstract

Abstract BACKGROUND: Chronic benign neutropenia, often referred as primary autoimmune neutropenia, is the most frequent cause of chronic neutrope-nia in children. Despite being a common and long known entity, evidence supporting its benign infectious course is scarce. More data would help guiding parents and clinicians in regard to patient evolution. OBJECTIVES: The aim of this study was to describe infectious episodes in children with moderate to severe autoimmune neutropenia supported by a normal bone marrow study. Secondary objectives were to determine the mean duration of the neutropenia and whether the severity of the neutro-penia was correlated to the development of severe infections. DESIGN/METHODS: We retrospectively reviewed medical records of patients with chronic neutropenia followed by a pediatric hematologist at our tertiary pediatric center, between November 1995 and December 2013. We only included patients with chronic benign neutropenia supported by a normal bone marrow. We excluded patients with immune deficiencies, genetic syndromes and metabolic diseases. Simple and multiple logistic regression were used to determine the association between the presence of severe infections and the absolute neutrophil count (ANC). We classified the severity of infection according to the medical literature. RESULTS: 84 medical records were retrospectively reviewed. 21 patients were excluded from the study based on exclusion criteria. We were able to collect complete data for 37 patients. The median age at diagnosis and at resolution was respectively 9 months (2mo-13yr) and 37 months (9mo-16y). The median duration of the neutropenia was 17 months (3mo-5y). During the neutropenic period, more than 112 mild infections were observed. 11 patients (29.7%) developed 13 moderate infections. 7 patients (18.9%) underwent 8 severe infections but no bacteremia was reported. ANC was not significantly different between patients who exhibited severe infections and those who did not (mean ANC=663±322×106/L vs 601±326×106/L; p=0.67). Recurrent infections occurred in 9 patients (24.3%). CONCLUSION: To our knowledge, our study is the largest on benign chronic neutropenia in children with normal bone evaluation. Severe infections have infrequently been reported in the literature for children with chronic benign neutropenia. Yet, almost 20% of our cohort exhibited at least one severe infection, although no bacteremia occurred. Interestingly, no association was found between the severity of the neu-tropenia and the presence of severe infection. We believe that these findings will help guiding the evaluation and management in this commonly occurring affection.