Comparison of Clinical Outcomes Between Adult and Pediatric Patients (pts) with Sickle Cell Disease (SCD): 3-Year (y) Follow-up in a Prospective, Longitudinal, Noninterventional Registry Trial
Authors: Heeney Matthew M. , Baltz Brad , Adams-Graves Patricia , Yang Elizabeth , Paley Carole , Esposito Jason , McNamara Katie , Vichinsky Elliott , George Alex 
Published: October 2019

Abstract
Introduction: Although advances in care have allowed individuals with SCD to live further into adulthood, treatment of adult SCD pts is challenging due to increased rates of comorbidities and complications. Here we present clinical outcomes and treatment patterns from a prospective registry of pediatric and adult pts with SCD at 3 y to better characterize disease and treatment patterns in adult pts.
Methods: Pts ≥2 y old with HbSS, HbSC or HbS/β-thalassemia were enrolled from 57 US centers and assessed every 6 mo until 3 y. Differences between pediatric (<18 y) and adult pts at 3 y are reported.
Results: Among 498 pts (317 pediatric; 181 adults) completing baseline visit, 74.1% had HbSS, 15.3% HbSC and 10.4% HbS/β-thalassemia; 61 pts discontinued the study. At baseline, pediatric pts had more asthma/airway reactive disease, dactylitis, and splenic sequestration (Table 1). Adults had significantly poorer performance status (P<0.0001) and more avascular necrosis (AVN), gallbladder disease (GBD), leg ulcers, and pulmonary hypertension (PAH). The most common SCD crisis was pain, both in the 5 y prior to study (86.2% of adults, 72.2% of children) and during study (64.1% of adults, 69.4% of children; Table 2). During study, more pediatric pts had respiratory conditions, including acute chest syndrome (ACS). More than half of all pts were hospitalized; key reasons were pain, fever, and ACS. Significantly more pediatric pts were hospitalized due to fever (P<0.0001) and significantly more adult pts were hospitalized for transfusion/chelation (P=0.0336). Absenteeism from school/work was frequent prior to and during study.
Conclusions: Patterns of disease and complications differed between children and adults. Adults had more hospitalizations due to transfusions/chelation and more classic chronic conditions (eg, AVN, GBD and PAH). Absenteeism from school/work was common in both groups. Limitations included the observational study design, variation in time from diagnosis, and lack of mandatory data collection.
TABLE 1. Baseline Characteristics of Pediatric vs Adult Pts with SCD at 3 Y <18 y(n=317) ≥18 y(n=181) Age, y, mean±SD 8.9±4.43 35.2±12.52* Males, % 56.8 47.0 SCD genotype, n (%) HbSS 242 (76.3) 127 (70.2) HbSC 43 (13.6) 33 (18.2) HbS/β-thalassemia 32 (10.1) 20 (11.0) Karnofsky performance status, n (%) 100% 105 (33.1) 26 (14.4)* 90% 64 (20.2) 54 (29.8)* ≤80% 22 (6.9) 63 (34.8)* Medical history, n (%) Aplastic episode 31 (9.8) 15 (8.3) Asthma/reactive airway disease 97 (30.6) 29 (16.0) AVN 10 (3.2) 61 (33.7) CNS Abnormal TCD 28 (8.8) 7 (3.9) Seizure 15 (4.7) 13 (7.2) Silent infarct 23 (7.3) 11 (6.1) Stroke (lifetime) 33 (10.4) 27 (14.9) Dactylitis 75 (23.7) 12 (6.6) GBD 48 (15.1) 80 (44.2) Leg ulcer 0 18 (9.9) PAH 3 (0.9) 19 (10.5) Splenic sequestration 75 (23.7) 15 (8.3)
*P<0.0001
 P<0.05
CNS, central nervous system; TCD, transcranial Doppler
TABLE 2. Clinical Complications and Treatment Patterns in Pediatric vs Adult Pts with SCD at 3 Y <18 y(n=317) ≥18 y(n=181) <18 y (n=317) ≥18 y (n=181) Clinical Complications Pts with SCD crises in 5 y prior to study, n (%) Pain 229 (72.2) 156 (86.2) Infections (≥1) 135 (42.6) 62 (34.3) ACS/pneumonia 135 (42.6) 40 (22.1) Stroke (lifetime) 33 (10.4) 27 (14.9) Priapism 14 (4.4) 14 (7.7) Pts with SCD crises in 3 y during study, n (%) Pain 220 (69.4) 116 (64.1) Infections (≥1) 113 (35.6) 53 (29.3) ACS/pneumonia 62 (19.6) 18 (9.9) Stroke 9 (2.8) 2 (1.1) Priapism 8 (2.5) 3 (1.7) Pts hospitalized in 3 y during study, n (%) 212 (66.9) 111 (61.3) Number of hospitalizations in 3 y during study, n Causesµ Pain 135 91 Fever 63 13  ACS/pneumonia 70 28 Transfusion/chelation 14 17 * Infections 8 7 Treatments Pts transfused, n (%) During 12 mo prior to study 138 (43.5) 96 (53.0)* During 3 y on study 172 (54.3) 93 (51.4) Chelation therapy, n (%) Pts ever chelated prior to study 63 (19.9) 59 (32.6)  During 3 y on study 40 (12.6) 19 (10.5) Pts used hydroxyurea, n (%) Prior to study 146 (46.1) 88 (48.6) During 3 y on study 156 (49.2) 78 (43.1) Absenteeism from school/work Missed school, n (%) Prior to study (>20 d in last 12 mo) 28 (14.7) 5 (25.0) During study (>20 d since last visit) 4 (2.5) 0 Missed work, n (%) Prior to study (>20 d in last 12 mo) 0 12 (22.2) During study (>20 d since last visit) 0 4 (9.5)
ACS, acute chest syndrome
*P<0.05
 P<0.01
 P<0.0001
µUp to 3 discharge diagnoses may be listed for any hospital admission

Disclosures
Heeney: Novartis: Research Funding. Adams-Graves:Novartis Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau. Paley:Novartis Pharma: Employment. Esposito:Novartis Pharma: Employment. McNamara:Novartis Pharmaceuticals Corporation: Employment. Vichinsky:Novartis : Consultancy, Research Funding, Speakers Bureau.