Identification and Clinical Characterization of Children with Benign Neutropenia

Introduction

Benign 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.

Methods

A 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.

Results

Searching 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.

Delayed 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.

Discussion

Compared 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.

Conclusion

BN 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.