Identification and Clinical Characterization of Children with Benign Neutropenia

Abstract

IntroductionBenign neutropenia (BN) is an asymptomatic condition observed in individuals of African descent. Patients with BN tend to have normal myeloid maturation within the bone marrow but release fewer neutrophils into the peripheral circulation. Previous studies of BN in pediatrics have reported no evidence of increased infections but otherwise lacked a detailed clinical description. The purpose of this study is to identify individuals with BN and better characterize the clinical findings seen in patients with this condition.MethodsA single institution retrospective study from 2008-2013 was conducted at an urban tertiary care children’s hospital in Washington, DC. Potential patients were initially identified by searching for ICD9 codes 288.0 (neutropenia) and 288.09 (neutropenia, not otherwise specified). Absolute neutrophil count (ANC) less than1500 was required for inclusion. Exclusion criteria included other hematologic disorder, pregnancy, low B12 or folate levels, prior cancer diagnosis, or concurrent immunosuppressant therapy. Demographic, laboratory, and clinical information on all included patients was recorded. All outpatient visits with a hematologist with a documented ANC were evaluated and recorded as encounters.ResultsSearching by ICD9 codes yielded 136 potential patients. 99 were excluded: 43 had antibody positive autoimmune neutropenia, 26 had transient or self-resolved neutropenia, 22 had concurrent malignancy, while 4 were receiving other immunosuppressant medications, and 4 had other known causes of neutropenia. The remaining 37 patients were included as BN, and were seen in a total of 130 encounters in the outpatient hematology clinic.Median age at evaluation was 5.3 years; 19 were males and 18 females. 22 (59.5%) patients were of African descent, 4 (10.8%) Caucasian, 3 (8.1%) Hispanic, 2 (5.4%) Asian, and 6 (16.2%) ethnicity was not documented. A summary of patient reported symptoms is in Table 1.Table 1Key clinical findings from BN individualsFindingPatients% ReportingUpper respiratory infection821.6Rash616.2Poor weight gain or weight loss410.8Headache38.1Oral ulcers38.1Bone or joint pain25.4Cervical lymphadenopathy25.4Gingivitis12.7Dental problems12.7Night sweats or chills12.7Delayed wound healing and dyspnea were not reported during by any patients. There were 2 patients with drug allergies and 1 with a food allergy. No first degree relatives of any of the patients were noted to have a history of neutropenia. For all patients in the study there were 5 total hospitalizations: 2 for febrile neutropenia, 1 each for mastoiditis, weight loss and neutropenia, and pneumonia. None of these hospitalizations required ICU management. 5 patients had bone marrow biopsies, 3 of which were normal and the others had focal/mild hypocellularity. In terms of laboratory findings, BN individuals had a median ANC of 893 x 10^6 cells per L. Additional laboratory statistical information can be seen in Table 2.Table 2Key laboratory results from BN individualsResultUnitsMinimum25th QuartileMedian75th QuartileMaximumWhite blood cellcells*109/L2.33.44.86.110.4ANCcells*106/L15862889312553614Neutrophils%71317.328.750.7Lymphocytes%37.453.767.470.781.1Monocytes%28.210.111.818Eosinophils%01.62.7412.4Hemoglobingm/dL9.411.311.812.714.1Hematocrit%26.432.73536.842.4Plateletscells*109/L170220265316472Immunoglobulin Gmg/dL445672104913511851Immunoglobulin Amg/dL2950106152203Immunoglobulin Mmg/dL226486112156DiscussionCompared to reported ANC values from patients with congenital neutropenias, BN patients in our sample rarely had ANCs < 500 and were hospitalized infrequently. The gender and racial characteristics of our study sample were atypical. BN has been previously reported to have a male predilection. A quarter of patients self-reported Caucasian, Hispanic, or Asian heritage – three backgrounds to which this clinical entity is quite atypical.ConclusionBN is often considered as a normal variant that does not confer increased risk of morbidity or mortality. Larger, prospective studies are needed to further elucidate the clinical course of this condition as well as to better understand molecular genetics. DisclosuresNo relevant conflicts of interest to declare.