Abstract
Patients (pts) with sickle cell disease (SCD) experience a heterogeneous clinical course, with a range of symptoms and sequelae. We describe clinical outcomes and treatment patterns from a prospective registry of pediatric and adult pts with SCD.
Pts ≥2 years old with HbSS, HbSC, or HbS/β-thalassemia were enrolled from 57 US centers and assessed every 6 months (mos) for up to 3 years. Differences between pediatric and adult pts at 24 mos follow-up are reported. (ClinicalTrials.gov NCT01220115).
A total of 498 pts completed the baseline visit (74.1% HbSS disease, 15.3% HbSC, and 10.4% HbS/β-thalassemia) (Table 1
| Table 1. Baseline Characteristics | ||
|---|---|---|
| <18 years (n=317) | ≥18 years (n=181) | |
| Age, years, mean ± SD | 8.9 ± 4.4 | 35.2 ± 12.5 |
| Males, % | 56 | 47 |
| SCD genotype, n (%) HbSS HbSC HbS/β-thalassemia | 242 (76.3) 43 (13.6) 32 (10.1) | 127 (70.2) 33 (18.2) 20 (11.0) |
| Karnofsky performance status, n (%) 100% 90% ≤80% | 106 (33.4) 72 (22.7) 24 (7.6) | 26 (14.4) 54 (29.8) 63 (34.8) |
| Medical history, n (%) Aplastic episode Asthma/Reactive airway disease Avascular necrosis CNS, abnormal TCD CNS, seizure CNS, silent infarct CNS, stroke (lifetime) Dactylitis Gallbladder disease Leg ulcer Pulmonary hypertension Splenic sequestration | 31 (9.8) 97 (30.6) 8 (2.5) 28 (8.8) 14 (4.4) 24 (7.6) 32 (10.1) 74 (23.3) 47 (14.8) 0 (0.0) 3 (0.9) 72 (22.7) | 15 (8.3) 29 (16.0) 61 (33.7) 7 (3.9) 13 (7.2) 11 (6.1) 27 (14.9) 12 (6.6) 80 (44.2) 18 (9.9) 19 (10.5) 15 (8.3) |
| Table 1. Baseline Characteristics | ||
|---|---|---|
| <18 years (n=317) | ≥18 years (n=181) | |
| Age, years, mean ± SD | 8.9 ± 4.4 | 35.2 ± 12.5 |
| Males, % | 56 | 47 |
| SCD genotype, n (%) HbSS HbSC HbS/β-thalassemia | 242 (76.3) 43 (13.6) 32 (10.1) | 127 (70.2) 33 (18.2) 20 (11.0) |
| Karnofsky performance status, n (%) 100% 90% ≤80% | 106 (33.4) 72 (22.7) 24 (7.6) | 26 (14.4) 54 (29.8) 63 (34.8) |
| Medical history, n (%) Aplastic episode Asthma/Reactive airway disease Avascular necrosis CNS, abnormal TCD CNS, seizure CNS, silent infarct CNS, stroke (lifetime) Dactylitis Gallbladder disease Leg ulcer Pulmonary hypertension Splenic sequestration | 31 (9.8) 97 (30.6) 8 (2.5) 28 (8.8) 14 (4.4) 24 (7.6) 32 (10.1) 74 (23.3) 47 (14.8) 0 (0.0) 3 (0.9) 72 (22.7) | 15 (8.3) 29 (16.0) 61 (33.7) 7 (3.9) 13 (7.2) 11 (6.1) 27 (14.9) 12 (6.6) 80 (44.2) 18 (9.9) 19 (10.5) 15 (8.3) |
CNS, central nervous system; SCD, sickle cell disease; TCD, transcranial doppler.
). At baseline, the following conditions were more frequent in adults: avascular necrosis, gallbladder disease, leg ulcers, and pulmonary hypertension. Pediatric pts had more frequent asthma/reactive airway disease, dactylitis, and splenic sequestration. The nature of sickle-related events varied between adult and pediatric pts (Table 2
| Table 2. Clinical Complications and Treatment Patterns | ||
|---|---|---|
| <18 years (n=317) | ≥18 years (n=181) | |
| Clinical Complications | ||
| Pts with SCD crisesa in 5 years prior to study, n (%) Pain† Infections (≥1)* ACS/Pneumonia ‡ Stroke (lifetime) Priapism (males) Pts with SCD crisesa in 24 mos on study, n (%) Pain Infections (≥1) ACS/Pneumonia Stroke Priapism (males) | 229 (72.2) 139 (43.8) 136 (42.9) 32 (10.1) 15 (8.4) 202 (63.7) 99 (31.2) 50 (15.8) 9 (2.8) 9 (5.0) | 156 (86.2) 62 (34.3) 40 (22.1) 27 (14.9) 14 (16.5) 110 (60.8) 50 (27.6) 16 (8.8) 2 (1.1) 3 (3.5) |
| Pts hospitalized in 24 mos on study, n (%) | 185 (58.4) | 96 (53.0) |
| Causesa | ||
| Pain | 113 (35.6) | 81 (44.8) |
| Fever* | 48 (15.1) | 13 (7.2) |
| ACS/Pneumonia | 55 (17.4) | 24 (13.3) |
| Transfusion/Chelation | 12 (3.8) | 14 (7.7) |
| Infections | 5 (1.6) | 6 (3.3) |
| Treatments | ||
| Pts transfused, n (%) During 12 mos prior to study During 24 mos on study | 139 (43.8) 145 (45.7) | 96 (53.0) 84 (46.4) |
| Chelation therapy, n (%) Pts ever chelated prior to study During 24 mos on study | 62 (19.6) 36 (11.4) | 59 (32.6) 14 (7.7) |
| Pts used hydroxyurea, n (%) Prior to study During 24 mos on study | 140 (44.2) 147 (46.4) | 88 (48.6) 79 (43.6) |
| Absenteeism, 12 mos prior to study, n (%) Missed school 1 to 10 days 11 to 20 days >20 days Missed work 1 to 10 days 11 to 20 days >20 days | 101 (51.0) 46 (23.2) 30 (15.2) 0 0 0 | 9 (45.0) 5 (25.0) 5 (25.0) 24 (44.4) 10 (18.5) 12 (22.2) |
| Table 2. Clinical Complications and Treatment Patterns | ||
|---|---|---|
| <18 years (n=317) | ≥18 years (n=181) | |
| Clinical Complications | ||
| Pts with SCD crisesa in 5 years prior to study, n (%) Pain† Infections (≥1)* ACS/Pneumonia ‡ Stroke (lifetime) Priapism (males) Pts with SCD crisesa in 24 mos on study, n (%) Pain Infections (≥1) ACS/Pneumonia Stroke Priapism (males) | 229 (72.2) 139 (43.8) 136 (42.9) 32 (10.1) 15 (8.4) 202 (63.7) 99 (31.2) 50 (15.8) 9 (2.8) 9 (5.0) | 156 (86.2) 62 (34.3) 40 (22.1) 27 (14.9) 14 (16.5) 110 (60.8) 50 (27.6) 16 (8.8) 2 (1.1) 3 (3.5) |
| Pts hospitalized in 24 mos on study, n (%) | 185 (58.4) | 96 (53.0) |
| Causesa | ||
| Pain | 113 (35.6) | 81 (44.8) |
| Fever* | 48 (15.1) | 13 (7.2) |
| ACS/Pneumonia | 55 (17.4) | 24 (13.3) |
| Transfusion/Chelation | 12 (3.8) | 14 (7.7) |
| Infections | 5 (1.6) | 6 (3.3) |
| Treatments | ||
| Pts transfused, n (%) During 12 mos prior to study During 24 mos on study | 139 (43.8) 145 (45.7) | 96 (53.0) 84 (46.4) |
| Chelation therapy, n (%) Pts ever chelated prior to study During 24 mos on study | 62 (19.6) 36 (11.4) | 59 (32.6) 14 (7.7) |
| Pts used hydroxyurea, n (%) Prior to study During 24 mos on study | 140 (44.2) 147 (46.4) | 88 (48.6) 79 (43.6) |
| Absenteeism, 12 mos prior to study, n (%) Missed school 1 to 10 days 11 to 20 days >20 days Missed work 1 to 10 days 11 to 20 days >20 days | 101 (51.0) 46 (23.2) 30 (15.2) 0 0 0 | 9 (45.0) 5 (25.0) 5 (25.0) 24 (44.4) 10 (18.5) 12 (22.2) |
P<0.05,
P<0.001,
P<0.0001, comparison between age groups.
Pts may have had multiple types of crises and causes for hospitalization.
ACS, acute chest syndrome ; SCD, sickle cell disease.
). Prior to study, adults had higher frequencies of pain crises, strokes, and priapism, while pediatric pts had more frequent infections and acute chest syndrome (ACS)/pneumonia. On study, a similar proportion of pediatric and adult pts (56.4% overall) were hospitalized, most frequently due to pain, fever, and ACS/pneumonia; a greater proportion of pediatric pts were hospitalized due to fever (P<0.05). The percentage of pts who received a transfusion and/or chelation while on study was similar between adult and pediatric pts. Almost half of the pediatric and adult groups received hydroxyurea prior to and during the study. High rates of absenteeism were observed, with 51% of pediatric pts and 44.4% of adults missing 1 to 10 days of school or work in the year before study.
Despite advances in care, SCD is associated with significant morbidity that contributes to high rates of hospitalization and absenteeism in both pediatric and adult pts. Continued follow-up in this registry will provide additional information about disease patterns and pt management.
Heeney:Novartis: Consultancy, Research Funding; Eli Lilly: Research Funding. Off Label Use: Hydroxurea is indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult patients with sickle cell anemia. It is not approved for use in children. Mueller:Novartis: Research Funding. Adams-Graves:Novartis: Consultancy, Speakers Bureau. Paley:Novartis: Employment. Esposito:Novartis: Employment. Katie:Novartis: Employment. Vichinsky:Novartis: Consultancy, Research Funding; ApoPharma: Consultancy, Research Funding; ARUP: Research Funding, Research Laboratory, Research Laboratory Other.
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