Introduction: Children with sickle cell disease (SCD) remain at higher risk for invasive infection with Streptococcus pneumoniae compared to the general pediatric population. Penicillin prophylaxis, pneumococcal conjugate (PCV), and polysaccharide vaccines (PPSV) have reduced the incidence of pneumococcal disease. Methods: A single institution cohort of children with SCD aged <19 years was reviewed over the 14-year period after PCV13 licensure (January 2010 – December 2023) to identify and characterize the clinical features and outcomes of S. pneumoniae bacteremia, including serotypes and antibiotic susceptibility. Results: The cohort included 4,356 children with SCD (24,076 person-years). Thirty-eight pneumococcal bacteremia cases were identified (32 HbSS, 5 HbSC, 1 HbSβ +-thalassemia), 21 (55%) in children age ≥5 years. The median time to culture positivity was 10.6 hours (range 3.4–20.2) from collection. Meningitis occurred in 4 (11%) and acute chest syndrome in 13 (34%). Serotype information was available for 36 (95%) isolates, which included 16 (44%) PPSV23 serotypes and 1 (2.6%) PCV13 serotype (serotype 3). Penicillin nonsusceptibility occurred in 12/31 (39%) at meningitis and 1/31 (3%) at non-meningitis breakpoints. Three (8%) deaths occurred (serotypes 12F, 23B, and 15B), all in children age ≥5 years, who had discontinued prophylactic penicillin. Long-term sequelae occurred in 5 (14%) surviving children, including hearing loss, limb amputation, motor and neurocognitive defects. Conclusion: Pneumococcal bacteremia continues to occur in children with SCD, with a risk of rapid progression to severe disease. Pneumococcal prevention strategies and urgent empiric treatment for fever remain important for children and adolescents of all ages with SCD.

Background There are sparse data on long-term and late effects of hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) Objectives To establish an international registry of long-term outcomes post-HCT for SCD and demonstrate the feasibility of recruitment at a single site in the US. Methods The STELLAR registry is designed to enroll SCD patients ≥ 1-year post-HCT, their siblings without SCD, and non-transplanted SCD controls to collect participant self-report of health status and practices using the BMT survivor study surveys, HRQOL using PROMIS 25 or 29, cGVHD using the symptom scale survey, daily pain using an electronic pain diary, economic impact of HCT using the financial hardship survey, and sexual function using PROMIS SexFSv2.0. We also piloted retrieval of clinical data previously submitted to CIBMTR, recorded demographics, height, weight, BP, hip and waist circumference, timed-up-and-go, and handgrip test, and obtained blood for metabolic screening, gonadal function, fertility potential, and biorepository of plasma, serum, RNA, and DNA. Results Among 100 eligible post-HCT patients, we enrolled 72 participants 9-38 (median 17) years age. We also enrolled 19 siblings 5-32 (median10)years age and 28 non-transplanted SCD controls 4-46 (median 22) years age. Of 119 participants, 73 completed 85 sets of surveys and 41 contributed samples to the biorepository. We successfully piloted retrieval of data submitted to CIBMTR and expanded recruitment to seven US, Canada, UK, and Nigeria sites. Conclusions It is feasible to recruit subjects and conduct study procedures for the STELLAR registry of long-term and late effects of HCT for SCD.

Introduction Pathophysiologic pathways of sickle cell disease (SCD) and air pollution involve inflammation, oxidative stress, and endothelial damage. It is therefore plausible that children with SCD are especially prone to air pollution’s harmful effects. Methods Patient data were collected from a single center, urban/peri-urban cohort of children with confirmed SCD. Daily ambient concentrations of particulate matter (PM 2.5) were collected via satellite-derived remote-sensing technology, and carbon monoxide (CO), nitrogen dioxide (NO 2), and ozone from local monitoring stations. We used multivariable regression to quantify associations of pollutant levels and daily counts of emergency department (ED) visits, accounting for weather and time trends. For comparison, we quantified the associations of pollutant levels with daily all-patient (non-SCD) ED visits to our center. Results From 2010-2018, there were 17 731 ED visits by 1740 children with SCD (64.8% HbSS/HbSβ 0). Vaso-occlusive events (57.8%), respiratory illness (17.1%), and fever (16.1%) were the most common visit diagnoses. Three-day (lags 0-2) rolling mean PM 2.5 and CO levels were associated with daily ED visits among those with SCD (PM 2.5 incident rate ratio (IRR) 1.051 (95% CI 1.010-1.094) per 9.4 µg/m 3 increase; CO 1.088 (1.045-1.132) per 0.5 ppm). NO 2 showed positive associations in secondary analyses; ozone levels were not associated with ED visits. The comparison, all-patient ED visit analyses showed lower IRR for all pollutants. Conclusions Our results suggest short-term air pollution levels as triggers for SCD events and that children with SCD may be more vulnerable to air pollution than those without SCD. Targeted pollution-avoidance strategies could have significant clinical benefits in this population.