Abstract: The randomized comparison of deferasirox to deferoxamine for myocardial iron removal in patients with transfusion‐dependent anemias ( CORDELIA ) gave the opportunity to assess relative prevalence and body distribution of iron overload in screened patients. Methods Patients aged ≥10 yr with transfusion‐dependent anemias from 11 countries were screened. Data were summarized descriptively, overall and across regions. Results Among 925 patients (99.1% with β ‐thalassemia major; 98.5% receiving prior chelation; mean age 19.2 yr), 36.7% had myocardial iron overload (myocardial T2* ≤20 ms), 12.1% had low left ventricular ejection fraction. Liver iron concentration (LIC) (mean 25.8 mg Fe/g dw) and serum ferritin (median 3702 ng/mL) were high. Fewer patients in the Middle East (ME; 28.5%) had myocardial T2* ≤20 ms vs. patients in the West (45.9%) and Far East (FE, 40.9%). Patients in the West had highest myocardial iron burden, but lowest LIC (26.9% with LIC 〈 7 mg Fe/g dw) and serum ferritin. Among patients with normal myocardial iron, a higher proportion of patients from the ME and FE had LIC ≥15 than 〈 7 mg Fe/g dw (ME, 56.7% vs. 17.2%; FE, 78.6% vs. 7.8%, respectively), a trend which was less evident in the West (44.6% vs. 33.9%, respectively). Transfusion and chelation practices differed between regions. Conclusions Evidence of substantial myocardial and liver iron burden across regions revealed a need for optimization of effective, convenient iron chelation regimens. Significant regional variation exists in myocardial and liver iron loading that are not well explained; improved understanding of factors contributing to differences in body iron distribution may be of clinical benefit.

Abstract: Severe congenital neutropenia is a rare disease, and autosomal dominantly inherited ELANE mutation is the most frequently observed genetic defect in the registries from North America and Western Europe. However, in eastern countries where consanguineous marriages are common, autosomal recessive forms might be more frequent. Method Two hundred and sixteen patients with severe congenital neutropenia from 28 different pediatric centers in Turkey were registered. Results The most frequently observed mutation was HAX1 mutation ( n  = 78, 36.1%). A heterozygous ELANE mutation was detected in 29 patients (13.4%) in our cohort. Biallelic mutations of G6PC3 ( n  = 9, 4.3%), CSF3R ( n  = 6, 2.9%), and JAGN1 ( n  = 2, 1%) were also observed. Granulocyte colony‐stimulating factor treatment was given to 174 patients (80.6%). Two patients died with infectious complications, and five patients developed myelodysplastic syndrome/acute myeloblastic leukemia. The mean (± mean standard error) follow‐up period was 129.7 ± 76.3 months, and overall survival was 96.8% (CI, 94.4–99.1%) at the age of 15 years. In Turkey, severe congenital neutropenia mostly resulted from the p W44X mutation in the HAX1 gene. Conclusion In Turkey, mutation analysis should be started with HAX1 , and if this is negative, ELANE and G6PC3 should be checked. Because of the very high percentage of consanguineous marriage, rare mutations should be tested in patients with a negative mutation screen.

Abstract: Sickle Cell Disease(SCD) is one of the most common hemoglobinopathies in the world which causes stroke. The management of stroke depends on the manifestations and the age of the patient. Especially in childhood, anatomic and physiological abnormalities of CNS may be a predisposing factors. Stroke mostly affects the distal segments of the Internal Carotid Artery, but also middle and anterior segments of the cerebral arteries are involved. The most important predisposing factors are the arterial malformations, stenosis and obstructions in cranial arteries, generally involving Internal Carotid Artery, frequently Proximal Middle Cerebral or Anterior Cerebral Arteries. After infarcts at brain vessels, most frequent clinical findings are hemiparesis or hemiplegia, impaired speech, focal seizures, gait disturbances. Risk factors for predisposing stroke are prior transient ischemia, baseline Hb decrease, acute chest sydrome within previous two weeks, systolic blood pressure rises, leucocyte increases. The patient with silent stroke or transient ischemic attacks may be asymptomatic or without neurological symptoms. Neuroimaging abnormalities may be seen without significant clinical findings in children with SCD. We talk about silent stroke if there are neuroradiological abnormalities without clinical findings. Children with silent strokes are more prone to new strokes. If there is a significant stroke a ischemic stroke often present with focal neurological signs and symptoms. If patient is asymptomatic or have suspected stroke, first step may be performance of Transcranial Doppler Ultrasonography (TCD). Children with time-averaged mean velocity (TAMV), measured in Middle Carotid Artery or in distal internal carotid Artery abnormally elevated, defined as TAMV ≥ 200 cm/sec, have sixfold increase for stroke than those with normal TAMV ≤ 170 cm/sec. For these patients under the risk of stroke, chronic blood transfusion is recommended for prevention of primary stroke events. Because of high oxygene demand in children, the child with SCD who also has anemia is at particular risk. The management of acute stroke includes to rule out hemorrhage, stabilize vital signs, careful use of hydration and RBCs transfusion. Exchange blood with normal RBCs is mandatory; it will improve tissue perfusion and oxygenation. Long-term management of stroke is directed to prevent recurrences with fluids supplementation, a chronic transfusion programme at least for 6 months with exchange transfusion or erythrocytapheresis for reducing the HbS under 30%. After 3 years of HbS levels to be maintained 〈 30%, the HbS leveles can be raised safely to less than 50% if the patient has remained neurologically stable. Indefinite chronic transfusion programme was advised for the patients with abnormal TCD values. Hydroxyurea (HU) is an alternative therapy in reducing TCD values and to try to increase HbF improving the clinical outcome. Periodical cranial Doppler ultrasound examination and selective red blood cell transfusions ‘d be useful for stroke prevention.镰状细胞病(SCD)是世上最常见的血红蛋白病，可致中风 中风防治受症状表现和病人的年龄所左右。 尤其对于患儿，中枢神经系统的组织异常和生理异常可能是诱病因素。 中风通常影响颈内动脉的末端，但也会牵连到脑动脉的中段和前段。 中风最重要的诱病因素有动脉畸形、器官狭窄和大脑动脉阻塞，一般和到颈内动脉有关，但牵连到大脑中动脉或大脑前动脉更为常见。 脑血管梗塞后，通常临床发现轻偏瘫或偏瘫、语言障碍、病灶性颠痫和步态障碍等。 诱病性中风具有的风险包括：前两周内引起短暂性局部缺血、血红蛋白含量减少和急性胸痛综合症，然后导致收缩压升高和白血球增加。 轻度中风或短暂性脑缺血发作的患者可能无症候或无神經症狀。 在没重大临床发现的情况下，镰状细胞病患儿可做脑神经成像检查，异常亦会发现。 下边我们将讨论无临床表现情况下神经放射性异常。 轻度中风的患儿再次中风的可能性很大。 如果中风严重，脑缺血的出现经常伴随着局部性神經系統症候和症状 如果患者无症候或疑似中风，首先应进行经颅多普勒超声（TCD）检查。 在异常抬升的中动脉或内动脉末端测量时间平均血流速度(TAMV)，结果为TAMV ≥ 200 cm/sec，该患者中风的可能性是正常情况（TAMV ≤ 170 cm/sec）的六倍。建议对有中风危险的患者采取慢速输血的方法，以防止主要中风事件。 由于儿童对氧的需求量高，患镰状细胞病同时伴有贫血的儿童危险系数尤其高。 急性中风防治的措施包括：排除溢血的可能性、稳定生命体征、谨慎利用水和作用和（血红细胞）RBCs输血 必须使用正常的RBCs交换血液；提高组织灌注和氧化作用。 中风的长期防治旨在阻止再次补充液体，用交换输血或红细胞除去法慢速输血至少6个月，以便把血红蛋白含量减少到30%以下。 血红蛋白含量 〈 30% 保持3年后，如果患者神经稳定，可将其升高到50%以下。 TCD值不正常的患者，建议采取不定期慢速输血程序。 作为降低TCU值的备用疗法，羟基脲（HU）尝试提高HbF的含量，达到改善临床结果的目的。 防止中风有效的措施包括定期对大脑进行多普勒超声检查和有选择性的进行血红细胞输血。

Abstract: Background and purpose: There are no currently approved treatments for the vaso-occlusive crises (VOC) associated with sickle cell disease (SCD). In addition to causing pain, vaso-occlusion and the resulting hypoxia cause a reduction in overall life expectancy and increase chronic morbidity. Sevuparin is a novel, non-anticoagulant, low-molecular weight heparin analogue, with a preclinical multi-modal activity profile against VOC relevant targets (i.e. P- and L-selectin, thrombospondin, Von Willebrand factor, fibronectin). Due to its low risk for bleeding side effects, sevuparin can be dosed at levels that were previously unattainable with heparinoids. The present study evaluated whether sevuparin could shorten the time with VOC in hospitalized SCD patients compared to placebo. Patients and methods: This phase II, global, multicenter, randomized, double-blind, placebo-controlled and parallel group clinical trial enrolled patients aged 12 to 50 with a diagnosis of SCD (HbSS, HbSC, HbSβ0-thalassemia, HbSβ+-thalassemia). The study recruited patients across 22 sites in 8 countries (Netherlands, Belgium, Turkey, Oman, Bahrain, Lebanon, Saudi Arabia, and Jamaica). Patients with VOC received sevuparin or placebo (1:1) along with standard of care (SoC) therapy with a requirement for parenteral opioid use. The primary endpoint was time to VOC resolution, measured as the time from IMP start until resolution by fulfilment of the two following criteria: a) freedom from parenteral opioid use (8 ± 2 hours), b) readiness for discharge as judged by the patient or physician (whichever occurred first). In addition to assessing safety, main secondary efficacy measures were related to pain and opioid use. The sample size of 120 VOC resolution events was determined based on an assumed between-arm hazard ratio of 0.60. Results: Overall, 147 subjects were randomized (144 dosed) to sevuparin, n=71 (69); or placebo n=76 (75). The median age of subjects entering the study was 22 years with 72% adults and 62,5 % males. Treatment groups were generally balanced with respect to demographic and baseline characteristics. Sevuparin, infused continuously at 18 mg/kg/day, did not confer any benefit over placebo in the primary endpoint of time to VOC resolution (ITT Cox proportional HR 0.89 (95% CI 0.61-1.30; p = 0.554; Figure 1a), which was also reflected by the secondary endpoint analyses (exemplified in Figure 1b). Most AEs were mild to moderate and transient. The number of SAEs was slightly higher in the placebo group (21/17 [22.4%]; one fatal case with hyperhemolytic crisis) than in the sevuparin group (16/15 [22.1%] ). The most commonly reported treatment emergent AEs (TEAEs) are displayed in Table 1. No clinically meaningful differences, imbalances or trends were apparent in TEAEs, laboratory parameters, vital signs, physical examination and ECG data across treatment groups. Conclusions: In this study, one of the largest VOC studies run to date, sevuparin failed to show an improvement of the VOC resolution time and associated measures (pain, opioid use, etc) in patients hospitalized with acute VOC. These results were surprising given both the promise from preclinical models and the clinical efficacy seen with selectin inhibition. It is possible that once full-blown, an acute VOC cannot be limited by sevuparin's mode of action (MoA). The understanding of sevuparin's MoA combined with this negative result may contribute to the notions of VOC causative factors and help inform future therapeutics targeting the VOC. The study is also important given its size and the high patient representation from the eastern Mediterranean and Middle Eastern regions, where SCD is of high prevalence. The comparison of this data with the available data from other VOC studies will be important in helping understand both regional and genetic differences in treatment practices and response to therapeutics. In conclusion, the present study showed that sevuparin treatment was not effective in acute VOC. However, sevuparin's promising safety profile and broad MoA including p-selectin inhibition, may warrant further exploration in the prodromal setting, especially given that sevuparin may be dosed by the patient at home in a convenient, subcutaneous format. Acknowledgements: Modus is grateful for the contributions from Ergomed, the Arabian Gulf University, the study sites, as well as to the patients for participating in this study. Disclosures Al-Khabori: Shire (Takeda): Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; NovoNardisk: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; SOBI: Honoraria; AstraZeneca: Honoraria. Abboud:CRSPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; GBT: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eli Lilly: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Other: Travel support; Modus: Research Funding; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Inati:Novonordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Research Funding; AstraZeneca: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kristensen:Modus Therapeutics: Employment. Donnelly:Modus Therapeutics: Employment. Ohd:Modus Therapeutics: Employment.

Abstract: Background: Patients with sickle cell disease (SCD) or other rare anemias whose care includes chronic blood transfusions must receive iron chelation to prevent the morbidity of iron overload. Currently, only deferoxamine (DFO) and deferasirox (DFX) are approved chelators in these patient populations. This randomized open-label trial evaluated if the efficacy of deferiprone (DFP) was non-inferior to DFO. DFO was used as the comparator product since DFX was not approved as first-line treatment for SCD at trial initiation. Methods: Participants at 27 sites in 8 countries were randomized in a 2:1 ratio to receive either DFP or DFO for up to 12 months. Those with lower transfusional iron input and/or less severe iron load were prescribed either DFP 25 mg/kg of body weight t.i.d. or DFO 20 mg/kg (children) or 40 mg/kg (adults); those with higher iron input and/or more severe iron load received either DFP 33 mg/kg t.i.d. or DFO up to 40 mg/kg (children) or 50 mg/kg (adults). Dosages could be adjusted over the course of the trial if necessary. Efficacy endpoints were the changes from baseline in liver iron concentration (LIC), cardiac iron, and serum ferritin (SF) at Month 12. The primary endpoint was based on LIC, and for the demonstration of non-inferiority of DFP to DFO, the upper limit of the 95% confidence interval for the difference between treatments had to be no more than 2 mg/g dry weight (dw). All patients had their neutrophil count monitored weekly, whereas other safety assessments and compliance with study therapy were evaluated monthly. Acceptable compliance was defined as taking 80% to 120% of the prescribed dosage. Results: A total of 228 of the targeted 300 patients were dosed with 152 receiving DFP and 76 receiving DFO, to assess non-inferiority. There were no significant differences between the groups in any demographic measures: in each treatment group, 84% of patients had SCD and the remainder had other, rarer forms of transfusion-dependent anemia. Mean age at enrollment was 16.9 years (± 9.6); 53.1% of patients were male; and 77.2% were white, 16.2% black, and 6.6% multi-racial. Over the course of the study, 69% of patients in the DFP group and 79% in the DFO group had acceptable compliance with treatment. Based on the Pocock's α spending function, a more stringent confidence level of 96.01% was applied to the calculation of confidence interval for the evaluation of non-inferiority. For the primary efficacy endpoint, the least squares (LS) mean change in LIC (measured as mg/g dw) was -4.04 for DFP, -4.45 for DFO; the upper limit of the 96.01% confidence interval for the difference was 1.57, thereby demonstrating non-inferiority of DFP to DFO. The upper limit for the subpopulation of patients with SCD also met the non-inferiority criterion. For the secondary endpoints, the change in cardiac iron (measured as ms on MRI T2*, log-transformed) was approximately -0.02 for both; and for SF (measured as μg/L), it was -415 vs. -750 for DFP vs. DFO, respectively. The difference between the groups was not statistically significant for both endpoints. With respect to safety, there was no statistically significant difference between the groups in the overall rate of adverse events (AEs), treatment-related AEs, serious AEs, or withdrawals from the study due to AEs. Agranulocytosis was seen in 1 DFP patient vs. no DFO patients, while events of less severe episodes of neutropenia occurred in 4 vs. 1, respectively. All episodes of agranulocytosis and neutropenia resolved. There was no significant treatment group difference in the rates of any of the serious AEs. Conclusion: The efficacy of DFP for the treatment of iron overload in patients with SCD or other rare anemias is not inferior to that of DFO, as assessed by changes in liver iron concentration. non-inferiority was supported by the endpoints on cardiac iron load and SF. The safety profile of DFP was acceptable and was similar to that previously seen in thalassemia patients, and its use was not associated with unexpected serious adverse events. The results of this study support the use of DFP for the treatment of iron overload in patients with SCD or other rare transfusion-dependent anemias. Note: The authors listed here are presenting these findings on behalf of all investigators who participated in the study. Disclosures Kwiatkowski: Terumo: Research Funding; Imara: Consultancy; bluebird bio, Inc.: Consultancy, Research Funding; Agios: Consultancy; Novartis: Research Funding; Celgene: Consultancy; Apopharma: Research Funding. Fradette:ApoPharma: Employment. Kanter:Sangamo: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Imara: Consultancy; Guidepoint Global: Consultancy; GLG: Consultancy; Cowen: Consultancy; Jeffries: Consultancy; Medscape: Honoraria; Rockpointe: Honoraria; Peerview: Honoraria; SCDAA: Membership on an entity's Board of Directors or advisory committees; NHLBI: Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc.: Consultancy; Modus: Consultancy, Honoraria. Tsang:Apotex Inc.: Employment. Stilman:ApoPharma: Employment. Rozova:ApoPharma: Employment. Sinclair:ApoPharma: Employment. Shaw:ApoPharma: Employment. Chan:ApoPharma: Employment. Toiber Temin:ApoPharma: Employment. Lee:ApoPharma: Employment. Spino:ApoPharma: Employment. Tricta:ApoPharma: Employment. OffLabel Disclosure: Deferiprone is an oral iron chelator.

Abstract: Introduction: Severe congenital nötropenia (SCN) is a very rare disease. Genetic mutation in neutrophil elastase gene (ELANE) is the most frequent mutation in European and North American registries. However, differences could be expected in the countries where consanguineous marriages are common. It is important to find out whether the approach for genetic typing shall be the same in western Europe, eastern Europe and middle East. We aimed to establish a national neutropenia registry in Turkey, a country with an extraordinary mixed population of Caucasian and Asian decent and the proportion of consanguineous families being higher than in most other parts of Europe. Patients and Methods: In this study, establishment of a national registry for severe congenital neutropenia (SCNR) and national bone marrow failure (BMFR) was aimed. Clinical and laboratory findings of 699 patients with BMF including 223 patients (31.9%) with SCN were entered into Turkish National BMFR. Results: The median age of the children with SCN (male/ female: 0.96) was 11.7 years (range 1 month to 35 years). The median follow up period for patients were 7.7 years (range 3 months to 34 years). Consanguinity between the parents of SCN patients was 36.3 %. HAX1 mutation was the most frequently seen mutation among the patients entered into national registry (n=51, 22.8%). The same mutation, homozygote c130-131insA, p.W44X, was detected in 47 of 51 patients (92.1%) with HAX-1 mutation. ELA2 mutation was detected in 16 patients (7.2%) and it was the second most common mutation for SCN. In this series 7 patients (3.1%) had a mutation in G6PC3 gene. CSF3R and JAGN1 mutations were seen in 4 (1.8%) and 2 (1.5%) patients respectively. No mutation was found in 66 (29.5%) tested patients (All tested for ELANE and HAX1 and 22 of them were also tested for G6PC3). Fifty two patients (22.4%) were not tested for SCN. Fifty eight percent of the patients were given GCSF. The median dose was 5 mcg/ kg for 3 days a week. Two patients died with infectious complications and six developed MDS/ AML. Conclusion: In Turkey SCN mostly resulted from the p W44X mutation in HAX1 gene. Therefore in Turkey mutation analysis should be started with HAX1 and if it is negative ELANE and G6PC3 should be checked. Rare mutations should be tested in mutation negative patients because of very high percentage of consanguineous marriage. This study was supported by TUBITAK and Turkish Pediatric Hematology Association. Disclosures Yilmaz Karapinar: TUBITAK: Research Funding.

Abstract: Abstract 996 The incidence of agranulocytosis during deferiprone (Ferriprox®) use has been reported in clinical trials where patients' neutrophil counts were generally monitored weekly and deferiprone was discontinued at the first sign of neutropenia (neutrophil count 〈 1.5 × 10 9/L), but the incidence in a less rigorously monitored environment is unknown. This observational, open label, prospective, multi-centre, non-interventional drug surveillance program was designed to assess how the safety of deferiprone therapy is monitored in clinical practice. All patients in the 15 participating treatment sites (Egypt, Oman, Saudi Arabia and Turkey) who initiated therapy with deferiprone during the observation period, were enrolled in the program. There were no exclusion criteria. The program was approved by local ethics boards and informed consent was obtained. 294 patients (53.4% males) were enrolled and the results of the first year of treatment are reported herein. Mean (SD) age of all patients was 12.2 ± 10.1 years (range 1 to 52 years old). 224 (76%) were children (93 of which were 1–5 years; 83 were 6–11 years and 48 were 12–17 years old). The majority of the patients had a diagnosis of Thalassemia Major (N= 261). The other patients had Thalassemia Intermedia (N=17), Sickle Cell Disease (N=9), Spherocytosis (N=3), Red Cell Aplasia/Diamond Blackfan Anemia (N=2), Immune Hemolytic Anemia (N=1) or Sideroblastic Anemia (N=1). Deferiprone was initiated as monotherapy (20 to 100 mg/kg/day) in 247 patients or added to deferoxamine therapy in 41 patients or to deferasirox in 6 patients. Serum ferritin was the common measure of iron overload in all 294 patients. Measurement of cardiac (CIC) and liver iron content (LIC) were conducted within 1 year prior to enrollment in 16 patients. Frequency of those measurements and the technique for those assessments varied among participating centers. CIC and LIC were assessed in 14 patients during the first year of follow up. At completion of 1 year of observation, the mean serum ferritin of the 282 patients who had a baseline and at least one follow up assessment had declined from 2858 ± 2481 to 2454 ± 2074 μg/L (p 〈 0.0001). Monitoring of the neutrophil count was conducted at an average interval of 5 ± 4 weeks (1 week to 6 months). One patient (0.3%) experienced agranulocytosis, which resolved with G-CSF 8 days after discontinuation of deferiprone. Ten patients (3.4%) experienced neutropenia (neutrophil count 〈 1.5 × 109/L but not 〈 0.5 × 109/L). One neutropenia was related to acute myeloid leukemia (AML). Deferiprone therapy was interrupted at diagnosis of AML, considered not related to DFP; and the patient was withdrawn from the program. Two patients had two episodes of neutropenia. All neutropenias, except the one associated with AML, resolved within 51 ± 48 days (range 8 to 167 days). Deferiprone therapy was continued in 7 episodes of neutropenia (time for resolution was 28 ± 24 days (range 8 to 67 days)). Deferiprone was interrupted in the remaining 4 episodes (time for resolution was 93 ± 55 days (range 35 to 167 days). None of the neutropenias progressed to agranulocytosis. The data from this observational study indicate that less frequent monitoring of the neutrophil count and continued deferiprone therapy during neutropenia was not associated with prolonged duration of the neutropenia or progression to agranulocytosis. Further evaluation of this observation is warranted. Disclosures: Elalfy: ApoPharma Inc.: Research Funding. Off Label Use: In USA, FERRIPROX® (deferiprone) is an iron chelator indicated for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate. Shebl:ApoPharma Inc.: Research Funding. Badr:ApoPharma Inc.: Research Funding. Elsafy:ApoPharma Inc.: Research Funding. Salama:ApoPharma Inc.: Research Funding. Al-Tonbary:ApoPharma Inc.: Research Funding. Abdel Rahman:ApoPharma Inc.: Research Funding. Qari:ApoPharma Inc.: Research Funding. Al Damnhouri:ApoPharma Inc.: Research Funding. Al Hawsawi:ApoPharma Inc.: Research Funding. Wali:ApoPharma Inc.: Research Funding. Yesilipek:ApoPharma Inc.: Research Funding. Kilinc:ApoPharma Inc.: Research Funding. Yazman:ApoPharma Inc.: Research Funding. Karakas:ApoPharma Inc.: Research Funding. Tricta:ApoPharma Inc.: Employment.

Abstract: Abstract 4824 Micro-RNAs are functional, non-protein coding RNA molecules and their transcriptions provided by intron or exon regions of the genome and non-protein coding regions of RNA genes. The role of micro-RNAs in acute leukemia has become the subject of research increasingly. In this study we aimed to identify micro-RNA profiles in the childhood acute leukemia that one of hematologic malignancies. Fourty nine patients who were diagnosed with acute leukemia and admitted to Cukurova University Faculty of Medicine Department of Pediatric Hematology between December 2010 and September 2011. Blood samples were taken twice in patient groups at diagnosis and during remission and plasma samples were stored. Blood samples were taken once in the healthy group and plasma were separated. The plasma samples were investigated by PCR analysis of micro-RNA. Acute leukemia was diagnosed by cytomorphological, immuno histochemical and flow cytometric studies. Thirtyone patients who were diagnosed with ALL and fortyseven healthy children as a control group were included to study. miR20a, miR25, miR92a, miR30c, miR106b, miR203, miR150, miR192, miR302c, miR184, miR218, miR320, miR342-3p, miR223, miR328, miR483-5p, miR376a, miR381, miR451, miR576-3p, miR548a levels were increased in newly diagnosed ALL patients when compared to healthy controls (p 〈 0.05). The miR20b, miR342-3p and miR548a levels were found higher in healthy controls than the newly diagnosed ALL patients group (p 〈 0.05) Healthy control groups when compared with pediatric ALL patients whose in remission; miR769-3p, miR20a, miR92a, miR16, miR27b, miR192, miR320, miR223, miR484, miR451 levels were found higher in healthy control groups than the patients. Newly diagnosed pediatric ALL patients compared with patients whose in remission; miR30c, miR106b, miR25, miR184, miR218, miR302c, miR483-5p levels were increased in newly diagnosed pediatric ALL patients than ALL patients whose in remission (p 〈 0.05). miRNAs are thought to be identified at a different level of expression in normal and pathological tissues can be determined between the miRNAs that are effective diagnosis and treatment of human cancers. We showed the microRNA profils that may play new roles treatment of acute leukemia in the futures. Disclosures: Kilinc: ApoPharma Inc.: Research Funding.

Abstract: Abstract 2228 Introduction: Novo Nordisk is developing turoctocog alfa, a human third generation recombinant FVIII for treatment of hemophilia A. During the pivotal trial in adult and adolescent previously treated patients with severe hemophilia A (guardian™1), subjects in need of surgery were able to participate in a subtrial to document efficacy and safety of turoctocog alfa in prevention of surgical bleeding. Pediatric ( 〈 12 years of age) previously treated patients in the guardian™3 trial were allowed to undergo minor surgery if needed during the trial. In addition, after completing these initial trials subjects were allowed to continue treatment with turoctocog alfa in the extension trial (guardian™2) which also includes a subtrial to document efficacy and safety of turoctocog alfa in prevention of surgical bleeding. Methods: We here describe surgeries performed within the guardian trials. For the ongoing guardian™2 extension trial, only cases included in the interim analysis (data cut-off 21NOV2011) are included. Results: In all, results from 10 major and 3 minor surgeries are included. Surgery indication was related to hemophilia joint disease in 8/13 cases. The hemostatic efficacy during and after surgery was rated on a 4-point scale (excellent, good, moderate and none) by the Investigator and/or Surgeon. Details and outcome of the individual surgeries performed are presented in Table 1. In addition, there were no safety concerns. Discussion: Prevention of surgical bleeding is an important aspect of hemophilia treatment. In the present 13 surgeries, including all surgeries performed with turoctocog alfa in the phase 3 guardian™ trials, hemostatic efficacy during and after was rated as either excellent or good in each case. The results support that turoctocog alfa has an excellent safety and efficacy profile for use in hemophilia A. Disclosures: Santagostino: Novo Nordisk and Pfizer: Research Funding; Pfizer, Baxter, Bayer, CSL Behring, Kedrion, Grifols and Novo Nordisk: Consultancy; Bayer, Baxter, Pfizer, CSL Behring, Novo Nordisk, Biotest, Kedrion and Grifols: Speakers Bureau. Lentz:Novo Nordisk: Consultancy, Research Funding. Brand:Bayer: Travel support, Travel support Other; Novo Nordisk, Baxter, Pfizer: Advisory Boards, Advisory Boards Other; Novo Nordisk: Honoraria. Chowdary:Novo Nordisk: Consultancy. Savic:Novo Nordisk: Speakers Bureau. Lindblom:Novo Nordisk A/S: Employment.