Chronic neutropenia (CN) encompasses multiple blood disorders with different etiologies resulting in absolute neutrophil counts (ANC) < 1500/µL for >3 months. To our knowledge, the association between annual incidence of serious infection events (SIEs) and severity of CN in the US has not been previously reported. Determine estimated annual incidence of SIE in people with CN with frequent SIEs (≥2/y), defined as events requiring hospitalization or intravenous antibiotics, or resulted in disability or death, in a real-world US population. This retrospective, cross-sectional cohort study identified people with ≥2 clinical visits and laboratory values recorded in the Dataworks USA Network electronic medical record (EMR) database for each calendar year from 2014–2019. To establish chronicity, people with CN were required to have ≥2 ANC tests < 1500/µL recorded in the 2 years before study entry. If frequent SIEs occurred, index date was defined as the second SIE of that calendar year of interest. General population was the non-neutropenic (ANC ≥ 1500/µL) EMR population who had ≥2 clinical visits and laboratory values. Neutropenia diagnoses were categorized using ICD-10 codes. People infected with HIV or receiving chemotherapy/drugs known to induce transient neutropenia were excluded. Primary outcome was annual SIE incidence in people with ≥2 ANC collected. Demographics are presented in Table 1. Annual estimated incidence rate of SIEs per 100,000 person-days for people with CN ranged between 51.1–83.4, 23.1–44.5, and 14.4–38.0 for ANC < 500/µL, 500– <1000/µL, and 1000–< 1500/µL, respectively, and was consistently 2-fold greater overall and 3- to 4-fold greater in people with severe CN (ANC < 500/µL) than general population (Figure 1). Increased estimated incidence of SIEs was observed in both age groups of people with CN evaluated, including pediatric (aged < 12 years) and adolescents/adults (aged ≥12 years).Download : Download high-res image (90KB)Download : Download full-size imageFigure 1. Incidence of Serious Infection Eventsa in a Real-World Population of People With CN Included in the Dataworks USA Network Between 2014 and 2019.ANC, absolute neutrophil count; CN, chronic neutropenia; COVID-19, coronavirus disease 2019. aSerious infection events were defined as diagnoses for any infection that required hospitalization or intravenous antibiotics, or resulted in disability or death.Table 1. (abstract: 189) Demographic and Laboratory Characteristics of People Included in the Analysisa, bEmpty Cell201420152016201720182019People in the database, N33,556,84638,127,26943,568,14350,741,23957,211,95563,145,385People included in the analysis'5, n43,21880,904100,330128,823145,924149,144Agec, n (%)<12 y4837 (11.2)9438 (11.7)11,906 (11.9)14,220 (11.0)15,434 (10.6)15,556 (10.4)≥12 y37,479 (86.7)70,034 (86.6)86,793 (86.5)112,803 (87.6)128,576 (88.1)131,696 (88.3)Sex at birthc,d, n (%)Male16,747 (38.8)31,508 (38.9)39,988 (39.9)51,008 (39.6)58,763 (40.3)60,696 (40.7)Female26,471 (61.2)49,394 (61.1)60,340 (60.1)77,805 (60.4)87,149 (59.7)88,434 (59.3)Racec, n (%)White34,089 (78.9%)61,234 (75.7)74,728 (74.5)92,038 (71.5)103,363 (70.8)104,811 (70.3)African American5665 (13.1)11,799 (14.6)14,787 (14.7)20,542 (16.0)23,142 (15.9)23,703 (15.9)Asian724 (1.7)1351 (1.7)1761 (1.8)2506 (2.0)2952 (2.0)3061 (2.1)Others102 (0.2)279 (0.3)382 (0.4)698 (0.5)815 (0.6)831 (0.6)Unknown2638 (6.1)6240 (0.4)8672 (8.6)13,039 (10.1)15,652 (10.7)16,738 (11.2)ANCc, n (%)<500/μL122 (0.3)237 (0.3)288 (0.3)408 (0.3)441 (0.3)479 (0.3)500–1000/μL205 (0.5)444 (0.5)622 (0.6)789 (0.6)908 (0.6)946 (0.6)1000–1500/μL762 (1.8)1513 (1.9)1938 (1.9)2464 (1.9)2841 (1.9)2926 (2.0)≥1500/μL42,129 (97.5)78,710 (97.3)97,482 (97.2)125,162 (97.2)141,734 (97.1)144,793 (97.1)ANC, absolute neutrophil count; CN, chronic neutropenia.aAll percentages were rounded to 1 decimal place.bIncluded people with CN who (1) did not receive chemotherapy nor (2) were treated with specific drugs that increase the risk of transient neutropenia prior to their first ANC < 1500/μL and people that were not neutropenic with ANC> 1500/μL.cPercentages may not equal 100 due to rounding.dSex unknown for <15 patients for each year. Figure 1. Incidence of Serious Infection Eventsa in a Real-World Population of People With CN Included in the Dataworks USA Network Between 2014 and 2019. ANC, absolute neutrophil count; CN, chronic neutropenia; COVID-19, coronavirus disease 2019. aSerious infection events were defined as diagnoses for any infection that required hospitalization or intravenous antibiotics, or resulted in disability or death. Table 1. (abstract: 189) Demographic and Laboratory Characteristics of People Included in the Analysisa, b ANC, absolute neutrophil count; CN, chronic neutropenia. All percentages were rounded to 1 decimal place. Included people with CN who (1) did not receive chemotherapy nor (2) were treated with specific drugs that increase the risk of transient neutropenia prior to their first ANC < 1500/μL and people that were not neutropenic with ANC> 1500/μL. Percentages may not equal 100 due to rounding. Sex unknown for <15 patients for each year. In this real-world analysis of US EMR data, people with CN were found to have a higher estimated annual incidence of SIEs compared with general population, providing evidence of the burden of SIEs in people with CN. To our knowledge, this is the first large EMR-based analysis of incidence of SIEs in both adults and children with CN in the US.