Children with SCD who were previously vaccinated with PPSV23 responded well to 1 PCV13 dose, and a second dose did not increase antibody response. PCV13 antibodies persisted above pre-vaccination levels for all serotypes 1 year after dose 2. Children with SCD may benefit from at least one dose of PCV13.

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The relationship between chronic hemolysis with subsequent iron overload, inflammation, and premature atherosclerosis has been documented in hemolytic anemias, particularly β-thalassemia. However, no such relationship has been established in sickle cell disease (SCD). We sought to evaluate SCD as a risk factor for early vascular insult by measuring carotid intima-media thickness (CIMT) and plasma chitotriosidase and to assess the role of the latter as a potential quantitative indicator of vascular inflammation and atherogenesis. Thirty SCD pediatric patients (3-18 years) and 30 matched controls were enrolled. Full clinical history, with hematological and biochemical parameters, was evaluated. CIMT and chitotriosidase activity were also assessed for all study participants. CIMT values were significantly higher in SCD patients (median 0.42; range 0.32-0.6 mm) compared to controls (0.36; 0.34-0.45 mm), P = 0.03. CIMT correlated positively with age (r = 0.460, P = 0.011), and total number of vascular incidents necessitating hospital admission (r = 0.439, P = 0.015). Similarly, chitotriosidase activity was significantly higher among SCD patients (median 59.6; range 7.3-512 nmol/ml plasma/h) compared to controls (32.7; 6.8-63.1 nmol/ml plasma/h), P < 0.001, and showed a positive correlation with serum ferritin (r = 0.517, P = 0.003) and CIMT (r = 0.535, P = 0.002). SCD children are at risk of developing premature atherogenic changes. Plasma chitotriosidase and CIMT may represent useful predictors of these changes.

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Sixty-five children with 76 hand anomalies had brachial angiography performed to help plan appropriate surgical management. Three different methods of angiography were used. The study showed that the direct exposure method is safe and simple, has few complications and gives the best visualisation of the arterial supply of the hand. It also showed that each type of congenital hand deformity is frequently associated with specific vascular alterations. Angiography is an important and safe investigation in the pre-operative assessment of cases of complex congenital hand deformities.

3212 Introduction: Children with sickle cell disease (SCD) have a significantly increased risk of invasive pneumococcal disease (IPD) and mortality, primarily attributable to functional asplenia. Penicillin prophylaxis and PPSV23 have been shown to dramatically reduce those risks, but strain resistance to penicillin has increased. Furthermore, PPSV23 is less effective in children <2 years and the protection declines within 3 years after administration. The introduction in 2000 of the 7-valent conjugate vaccine (PCV7) induced a further reduction of IPD in children with SCD, but was accompanied by the emergence of non-PCV7 serotypes-related IPD, especially 19A. A new PCV13 incorporating the new serotypes 1, 3, 5, 6A, 7F and 19A to those in PCV7 was recently licensed. This study was designed to determine whether PCV13 has the potential to offer immunologic benefit to children with SCD. Methods: We conducted a phase 3, open-label, single-arm study to evaluate the safety, tolerability, and immunogenicity of 2-doses of PCV13 given 6 months apart to children 6 to less than 18 years of age with SCD previously immunized with PPSV23 more than 6 months prior to study entry. Blood samples were collected prior to and 1 month after each dose. Serotype-specific immunoglobulin (IgG) geometric mean concentrations (GMCs) and fold rises (GMFRs) were determined. Local pain, redness and swelling, and fever, vomiting, diarrhea, headache, fatigue, muscle pain and joint pain were recorded in an ediary for 7 days after each dose. Serious adverse events (SAEs) were reported throughout the study. Results: We enrolled 158 subjects; 51.9% were males. All subjects were previously vaccinated with PPSV23; 12 subjects had received 2 to 6 doses. The mean age at enrollment was 13.3 (±3.08) years. All subjects received dose 1; 146 subjects received dose 2. One of the 12 subjects who did not complete the vaccination phase withdrew due to local pain and systemic events reported after dose 1. Subjects responded very well to a single dose of PCV13 (see Table). The prevaccination/postdose 1 IgG GMFRs ranged from 1.73 (serotype 5) to 7.01 (serotype 4). The antibodies declined over 6 months and subjects responded well to a second dose of PCV13; however the IgG GMCs were generally lower than after the first dose (see Table). The postdose 2/postdose 1 IgG GMFRs were <1.0 for all serotypes except 19F and the 95% confidence intervals did not include 1.0 except for serotypes 6A, 6B, 19F and 23F, suggesting the postdose 2 responses were significantly lower than postdose 1. 91.7% and 88.5% of subjects reported local reactions, and 87.5% and 89.3% of subjects reported systemic events after dose 1 or dose 2, respectively. Most of the SAEs were due to vaso occlusive crisis and only one was assessed by the investigator as related to the study vaccine. No deaths occurred. Conclusions: Children with SCD previously vaccinated with PPSV23 responded well to PCV13. A second dose did not enhance the immune response, likely due to the short interval (6 months) and high levels of persisting antibody. Pending analysis of functional antibody responses assessed by opsonophagocytic activity (OPA) will further describe the immune responses of PCV13 in this population. Disclosures: De Montalembert: Novartis: Speakers Bureau. Abboud:Novartis: Speakers Bureau. Fiquet:Vaccines Clinical Research Pfizer Global Research and Development : Employment. Piga:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Jiang:Pfizer Inc: Employment. Pereira:Vaccines Clinical Research Pfizer Global Research and Development: Employment. Emini:Pfizer Inc.: Employment, Equity Ownership. Gruber:Pfizer: Employment. Gurtman:Pfizer: Employment. Scott:Pfizer: Employment.

Introduction While the mechanism of bone disease in thalassemia is multifactorial and still under investigation, the receptor activator of nuclear factor kappa B (RANK), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) have pivotal roles in regulating bone metabolism. This study aimed to measure RANKL and OPG serum levels, and to detect the incidence of RANKL rs9533156, OPG rs2073618, and OPG rs2073617 genotypes in pediatric β‐thalassemia patients and to assess their relation to bone mineral density. Methods Sixty patients with transfusion‐dependent β‐thalassemia (TBT) patients ages 5 to 14 years were included, and 60 healthy, age‐ and sex‐matched volunteers contributed as a control group. The patients were scanned for bone mineral density. Results The mean of spine dual‐energy X‐ray absorptiometry (DXA) Z‐score in patients was −1.66 ± 1.02 standard deviation (SD). Twenty‐four of them had low spine DXA Z‐scores. The patients showed significantly lower OPG levels and OPG/RANKLs ratios than the control group (3.28 ± 9.11 ng/ml and 11.38 ± 14.93 ng/ml, and 0.01 ± 0.03 and 0.07 ± 0.09, respectively). The RANKL SNP rs9533156 TC heterozygous genotype was detected more with statistical significance in patients than controls. The incidence of OPG rs2073618 and OPG rs2073617 genotypes were 2.3 times and 1.9 times more frequent in patients than controls, respectively. Conclusion The RANK/RANKL/OPG system may have an important role in regulating bone metabolism in TBT patients, although further studies are needed to clarify its role.