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Objectives: Critical illness in COVID-19 is attributed to an exaggerated host immune response. Since neutrophils are the major component of innate immunity, we hypothesize that the quantum of activated neutrophils in the blood may predict an adverse outcome. Design: In a retrospective study of 300 adult patients with confirmed COVID-19, we analyzed the impact of neutrophil activation (NEUT-RI), interleukin-6 (IL-6) and the established clinical risk factors of age, diabetes, obesity and hypertension on the clinical outcome. Results: Significant predictors of the need for mechanical ventilation were NEUT-RI (Odds Ratio (OR) = 1.22, P < 0.001), diabetes (OR = 2.56, P = 0.00846) and obesity (OR = 6.55, P < 0.001). For death, the significant predictors were NEUT-RI (OR = 1.14, P = 0.00432), diabetes (OR = 4.11, P = 0.00185) and age (OR = 1.04, P = 0.00896). The optimal cut-off value for NEUT-RI to predict mechanical ventilation and death was 52 fluorescence intensity units (sensitivity 44%, specificity 88%, area under the curve 0.67 and 44%, 86%, 0.64, respectively). Conclusion: This finding supports an aberrant neutrophil response in COVID-19, likely due to uncontained viral replication, tissue hypoxia and exacerbated inflammation, introduces a novel biomarker for rapid monitoring and opens new avenues for therapeutic strategies.

Objectives Most literature on the frequencies of red blood cell (RBC) phenotypes are published in Europeans and Africans countries, with the frequencies in the Omani population unknown. We sought to determine the prevalence of RBC blood group phenotypes among Omani blood donors. Methods Blood group ABO, RhD type, and phenotyping were performed for 21 blood group antigens on enrolled blood donors. The following antigens were assessed serologically: Rh (C, c, E, e), Kell (K, k, Kpa, Kpb), Kidd (Jka, Jkb), Duffy (Fya, Fyb), Lewis (Lea, Leb), Lutheran (Lua, Lub), MNS (M, N, S, s), and P1. Results A total of 337 Omani blood donors were tested. The most common blood group was O+ (44.9%). Among the tested blood donors studied, 89.3% were RhD positive with R1r being the most common Rh phenotype. The k antigen was found at a frequency of 99.4%, while 4.5% of the blood donors studied were K+. The most common phenotype in the Duffy blood group system was Fy(a-b-), while the most common phenotypes in the Kidd and MNS blood group systems were Jk(a+b+) and M+N-S+s+ at 47.0% and 22.6%, respectively. The Le(a+) and Le(b+) antigens were found in 21.7% and 67.3% of the blood donors, respectively. One Jk(a-b-), one Le(a+b+), and two Lu(a-b-) individuals were identified. Conclusion This is the first study to examine the frequencies of RBC phenotypes among the Omani blood donors. The study's results show Duffy blood group frequencies that resemble what has been reported in the African population, and higher frequencies of the rare null phenotypes compared to European populations.

Natural killer (NK) cell lymphoproliferative disorders are uncommon and the Epstein-Barr virus (EBV) plays an important aetiological role in their pathogenesis. We report a 20-year-old male with a chronic active EBV infection associated with a NK cell lymphoproliferative disorder which had an unusual indolent course. He presented to the Sultan Qaboos University Hospital in Muscat, Oman, in December 2011 with a history of intermittent fever and coughing. Examinations revealed generalised lymphadenopathy, hepatosplenomegaly, leukocytosis, transaminitis, diffuse bilateral lung infiltrates and bone marrow lymphocyte involvement. A polymerase chain reaction (PCR) test revealed a high EBV viral load in the peripheral blood cells. The patient received a course of piperacillin-tazobactam for Klebsiella pneumoniae , but no active treatment for the lymphoproliferative disorder. However, his lymphocyte count, serum lactate dehydrogenase and liver enzymes dropped spontaneously. In addition, EBV PCR copies fluctuated and then decreased significantly. He remained clinically asymptomatic over the following four years. Keywords: Epstein-Barr Virus Infections; Natural Killer Cell; Lymphoproliferative Disorders; Spontaneous Remission; Case Report; Oman.

Introduction: Von Willebrand Disease (VWD) is the second most common inherited bleeding disorder. There is paucity of the literature describing the prevalence and clinical characteristics of VWD in this part of the world. The aim of the current study is to detect the prevalence, describe the spectrum of the different types of VWD, their mode of presentation, bleeding phenotype and outcome in Oman. Methods: A retrospective cross-sectional study was carried out in the 2 available referral tertiary care facilities in Oman namely; Sultan Qaboos University and the Royal Hospitals. The study included all children and adults diagnosed with VWD in Oman until June 2019. The patients were subtyped as per the International Society of Thrombosis and Haemostasis (ISTH) criteria. Data was collected from the electronic hospital systems in both hospitals. Out of 700 entries of VWD in both hospitals, only 140 were true cases and 560 were tested negative but wrongly labelled. Patients or their next of ken were called and interviewed to obtain the necessary information that was not documented in the electronic system. Results: A total of 140 patients are confirmed to have VWD giving a prevalence of 1:20000. Fifty eight patients are males (41.5%), 82 patients are females (58.5%). Sixty six patients have type I (47%), 38 patients have type II (27%) and 36 patients have type III (26%). The majority of patients 90 (64%) were diagnosed before the age of 20 years and 62 of them (68%) had positive family history of the disease. The most common presentation was recurrent unexplained bruising. As expected, patients with type III tend to have a significant bleeding phenotype with a bleeding score more than 5 in adults and 3 for paediatric patients. All of them were admitted to hospital at some point electively (for surgery) or for bleeding control, however, they were not put on prophylaxis. None of the patients had serious or intra-cranial bleeding. Conclusion: Von Willebrand Disease is not uncommon in Oman with an overall prevalence of 1:20000, however, it is much less than what was originally reported in previous studies in developing countries and the WFH website. The majority of patients are type 1 and have a positive family history of the disease. The disease is more common in females. All patients with type III have abnormal bleeding score and required VW factor replacement at one point. None of the patients had a serious bleed and they are not on prophylaxis. Keywords: Von Willebrand disease, Prevalence, Oman. Disclosures Al-Khabori: AstraZeneca: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; SOBI: Honoraria; NovoNardisk: Membership on an entity's Board of Directors or advisory committees; Shire (Takeda): Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

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.

Objectives: Sickle Cell Disease (SCD) is an inherited hemoglobinopathy with multiple complications including stroke. It is observed that siblings with SCD have an increased risk of stroke if there was a sibling in the family with SCD and stroke (Driscoll M C, Blood, 2003). Human Leukocyte Antigen (HLA) is extremely variable among individuals and certain HLA alleles have previously been associated with a number of diseases. It has been shown that HLA-DRB1*0301, HLA-DRB1*0302 and HLA-DQB1*0201 increase the risk of stroke and HLA-DRB1*1501 and HLA-DQB1*0602 lower the risk of stroke in patients with SCD (Styles L, Blood, 2000). These alleles are not common in all populations. We therefore planned to assess the impact of other HLA alleles on the risk of stroke in patients with SCD. Methods: This is a retrospective case-control study conducted at Sultan Qaboos University Hospital. We included all adult and pediatric patients with SCD and diagnosed with stroke using CT/MRI of the brain. The study included patients diagnosed during the period of 1995 to 2015. HLA typing was performed using molecular techniques. HLA alleles with a frequency of at least 5% were selected for analysis. Association studies were performed using Fisher Exact test. All statistical tests were performed using R program (version 3.1.2). Results: A total of 244 patients were included (66 patients with SCD and stroke [cases] and 178 patients with SCD with no stroke. The median age was 26 years (Interquartile Range [IQR]: 19-32) and 23 (IQR: 17-29 ) for cases and controls respectively. The median hemoglobin, mean corpuscular volume, hemoglobin S level and lactate dehydrogenase level was 9 g/dL, 70 fL, 70% and 400 U/L respectively for the cases, and 9 g/dL, 60 fL, 70% and 400 U/L respectively for the control. The most frequent HLA-A allele was HLA-A*02 (24%) which did not impact the risk of stroke (Odds Ratio [OR]: 1.59, 95% Confidence Interval [CI]: 0.84-3.02) as were the other tested HLA-A alleles (all CIs crossed OR of 1.00). The most frequent HLA-B allele was HLA-B*51 (15%) which did not impact the risk of stroke (OR: 0.89, 95% CI: 0.43-1.85) as were the other tested HLA-B alleles (all CIs crossed OR of 1.00). The most frequent HLA-C allele was HLA-C*04 (17%) which did not impact the risk of stroke (OR: 1.34, 95% CI: 0.67-2.65); however, HLA-C*06 (OR: 2.37, 95% CI: 1.01-5.54) increased the risk of stroke while HLA-C*07 protected from stroke (OR: 0.35, 95% CI: 0.13-0.93). None of the other HLA-C alleles were statistically significant (all CIs crossed OR of 1.00). The most frequent HLA-DRB1 allele was HLA-DRB1*16 (18%) which did not impact the risk of stroke (OR: 1.02, 95% CI:0.51-2.03) as were the other tested HLA-DRB1 alleles (all CIs crossed OR of 1.00). Conclusions: HLA-C*06 is associated with an increased risk of stroke in patients with SCD while HLA-C*07 is protective from stroke in these patients. Early identification of high-risk patients would be beneficial for preventive intervention, such as chronic transfusion or bone marrow transplantation. The impact of these HLA alleles should be validated in other populations. Disclosures Al-Khabori: Shire (Takeda): Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; SOBI: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; NovoNardisk: Membership on an entity's Board of Directors or advisory committees; Roche: 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.

Objectives: Distinguishing between acute presentations of osteomyelitis (OM) and vaso-occlusive crisis (VOC) bone infarction in children with sickle cell disease (SCD) remains challenging for clinicians, particularly in culture-negative cases. VOC and osteomyelitis have a very similar presentation in the acute stage, and both are associated with a rise in C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR). The gold standard to diagnose osteomyelitis is obtaining a positive blood culture and bone/joint biopsy which is invasive and not frequently done. Standard magnetic resonance imaging (MRI) with fat suppression sequencing (subtraction technique) may help to confirm osteomyelitis in SCD patients; however, this is frequently not done in a timely manner and is associated with false positive and false negative results. The objective of this study is to assess the discriminative impact of baseline variable and build a score to assess the diagnosis of osteomyelitis in pediatric patients with SCD. Methods: A retrospective study of all patients with SCD, aged 1 to 18 years old with suspected osteomyelitis. The study covered a period of over 4 years (January 2015- June 2019) at Sultan Qaboos University Hospital, which is the main tertiary care and referral facility in Oman. All the patients were subjected to a complete clinical assessment, laboratory blood tests including, CBC, CRP, blood and aspirated fluid (if applicable) culture, and standard MRI with fat suppression sequencing of the affected bone. A clinical and laboratory score was designed to test whether it can help to prove or disprove the diagnosis in likely cases (Table 1). Results: A total of 43 patients fulfilled the inclusion criteria. Their mean age was 8.7 years +/-3.4. Male to female ratio was 1.87:1. All patients have been initiated on antibiotic therapy as osteomyelitis based on the clinical suspicion and MRI findings. The mean score in the 11 patients with confirmed osteomyelitis was 11/13. Thirteen patients were classified as likely osteomyelitis. Their mean score was 7.5/13. Seventeen patients were confirmed to have VOC by the clinical course (fast resolution of fever, local signs of inflammation and the drop in inflammatory markers). Their mean score was 5.7/13 (Table 2). Conclusion: Differentiating VOC from osteomyelitis in children with SCD who present with fever and bone pain is a difficult task. Our proposed score assigned different mean score to different clinical entity (confirmed OM vs. likely OM vs. VOC). This score may assist clinicians to differentiate these entities. A larger prospective study is needed to confirm and validate the score. Disclosures Tbaileh: Sultan Qaboos University Hospital: Other: Data Collection, Data Input , Discussion of data with my seniors. Al-Khabori:Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: 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; SOBI: Honoraria; AstraZeneca: Honoraria; NovoNardisk: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Shire (Takeda): Membership on an entity's Board of Directors or advisory committees. Wali:Sultan Qaboos University Hospital: Employment.

Background: Sickle cell disease is a common hemaglopinapthy worldwide and in Oman. Avascular necrosis (AVN) of the hip causes significant morbidity to patients with sickle cell disease and has a profound impact on their quality of life. This study aims to identify the prevalence and outcome of AVN among young Omani patients with sickle cell disease. Methods: The is a cross sectional study done in the main tertiary care and referral facility in Oman, Sultan Qaboos University Hospital. Out of 3000 registered patients 85 patients found to have clinical and radiological proven AVN, between June 2017-January 2019. Data obtained included demographics, the affected joint, uni or bilateral), radiological staging by FICAT (MRI), hydroxyurea use, dose and duration as well as laboratory data at time of diagnosis. Results: The prevalence of AVN among SCD Omani children and young adults is 2.8 %. Their age ranges between 5-25 (Mean 14.6 +3.4). Male to female ratio was 1.6:1. Based on FICAT system score, most of the cases (82%) are AVN grade 3 and above at diagnosis. Thirty-six patients (42%) were diagnosed to have stage IV AVN. Regarding the hydroxyurea use, 43 patients (50.6%) were already started on HU before the development of AVN. Their mean duration of HU use was 5.3 years, with an average dose of 15.7 mg/kg/day. Fifteen patients developed AVN and were started on HU as part of their management. The follow up MRI of 4 of them showed improvement of their AVN stage (from 4 to 2). Fifteen patients (17.6%) underwent joint replacement because of chronic pain and disability and almost half of them (7 patients) were on hydroxyurea. Conclusion: Prevalence of AVN in young patients with SCD in the main tertiary care referral facility in Oman is 2.8% which is less than the internationally reported. Patients are diagnosed at later stages (3 and above) indicating a possibility of underdiagnosis of asymptomatic stage one and 2 patients. Hydroxyurea use has improved the severity of the AVN in few patients. Disclosures Al-Khabori: SOBI: Honoraria; AstraZeneca: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; 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; NovoNardisk: Membership on an entity's Board of Directors or advisory committees. Wali:Sultan Qaboos University Hospital: Employment.

Objectives: Mutations in epigenetic modifiers including IDH (Isocitrate dehydrogenase), DNMT3A (DNA Methyltransferase 3 Alpha), TET2 (Ten-Eleven Translocation 2), ASXL1 (Additional Sex Combs-Like 1), and EZH2 (Enhancer of Zeste Homolog 2) have been recently recognized in patients with Acute Myeloid Leukemia (AML). The DNMT3A and IDH were found to be associated with poor prognosis in most studies; however, there is no meta-analysis evaluating other mutations in the epigenetic modifiers. We performed a systematic review and meta-analysis to evaluate the prognostic significance of mutations in the epigenetic modifiers on the Overall Survival (OS) of patients with AML. Methods: We searched for studies evaluating epigenetic mutations in AML (up to August 2018) in PubMed. Two reviewers independently screened all citations and later abstracted data using a common data collection form. Risk of bias was assessed using Newcastle-Ottawa Scale (NOS) and Cohen kappa coefficient (k) was calculated to assess the agreement. Hazard ratio (HR) and 95% confidence interval (CI) of outcomes were extracted and random effects model was used to pool the results. Statistical heterogeneity was calculated using Cochran I2 and tested using chi-squared tests. Results: A total of 9543 citations were retrieved from the search strategy; of which 9415 were excluded after title screening and 37 articles were excluded after abstract screening. A review of full text excluded additional 49 articles for incomplete data and missing analysis on OS. Forty-two articles were identified for the systematic review and meta-analysis (IDH n=15, DNMT3A n=12, TET2 n=8, ASXL1 =7), all of which were fair to good quality studies based on the NOS. The analysis of IDH mutation included 15 articles covering 5100 patients with a median age of 55 years. The frequency of IDH mutations ranged from 7 to 33%. The pooled HR indicated that IDH mutation conferred significantly worse OS (HR = 1.54; 95% CI: 1.15-2.06) though with a substantial heterogeneity (I2 = 85%). Mutation analysis of DNMT3A was based on 12 articles including 5418 patients with a median age of 52 years. The proportion of patients with this mutation ranged from 14 to 34%. Results indicated a worse OS with a pooled HR of 1.35; 95% CI 1.16-1.56, and a substantial heterogeneity (I2=71%). For the ASXL1 mutation, our analysis included 4115 adult and pediatric patients from 7 studies. The pooled HR indicated that ASXL1 mutation conferred a significantly worse OS (HR = 1.88; 95% CI: 1.49‒2.36); however, with a moderate heterogeneity (I2 = 43%). The TET2 mutation analysis was based on eight studies with a total of 3286 patients. The pooled HR indicated that TET2 mutation conferred a significantly worse OS (HR = 1.39; 95% CI: 1.18‒1.63); with a low heterogeneity (I2 = 28%). Conclusions: Epigenetic mutations in IDH, DNMT3A, ASXL1 and TET2 adversely impact OS in patients with AML. These mutations in the epigenetic modifiers should be considered in the initial evaluation of patients with AML and in the decision on post induction management. 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; SOBI: Honoraria; AstraZeneca: Honoraria; NovoNardisk: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Objectives: To assess the response rate and duration of response in patients with chronic immune thrombocytopenia (ITP) receiving rituximab. Methods: We retrospectively analyzed 32 consecutive patients with chronic ITP who were treated in two tertiary centers in Oman. Response assessment was based on the American Society of Hematology criteria. Results: Nineteen patients (59%) had an initial response. However, six of the 19 patients lost their response leaving 13 patients with long-lasting remissions. The median age at diagnosis was 25 years (range 14–58). The median time from diagnosis to rituximab therapy was 21 months. The median follow-up after starting rituximab was 26 months. The overall cumulative response rate was 59% (complete response 44%, partial response 15%) and the median time to respond was 30 days with a response rate of 44% at four weeks. In all responders, the cumulative rate of loss of response was 32% with a median time to lose response of 54 months. Conclusions: The use of rituximab in ITP achieves high response rate and long remission duration. Our study was limited by the small sample size and further larger prospective studies are recommended.

Background: In spite of guidelines recommending the no need for coagulation profile prior to ENT surgeries when challenging history of bleeding is negative, yet surgeons still practice it. Cost and delaying surgeries are major issues faced when insignificant abnormalities are found in the coagulation profile results. In 2008, British Committee for Standards of Hematology has published guidelines (1) on assessing the bleeding risk prior to surgeries or invasive procedures, which stated that the indication for sending a coagulation profile is best based on the bleeding history of the patient. Aim: This study aimed to measure unbiased estimate of hemostatic outcomes in ENT surgeries in relation to coagulation testing. Methods: All patients who underwent ENT surgeries from three tertiary hospitals during the period from 1st July 2016 to 1st January 2017 were enrolled in the study. The retrieved data included gender, age, type of surgery, results of coagulation blood test (if done), other laboratory test results (complete blood count, biochemical profile, etc.), postoperative bleeds, how it was managed, need for blood transfusion and whether the patient required another surgery to stop the bleeding or not. Patients with known bleeding history or previous coagulation derangement were excluded from the study. The primary outcome was post-operative bleeding. Results: The study included data from 730 patients who underwent ENT surgical procedures. They were 432 males and 298 females. Their mean age was 19.6 + 16.92 year. Out the 730 patients, 372 patients were interviewed for a challenging bleeding history alone (group 1) and 358 were interviewed plus a pre-operative coagulation profile check (Group 2). Total of fourteen patients (1.9 %) developed postoperative bleeding. None of them was due to abnormal bleeding tendency and they didn't require any hemostatic support. Six of them bled early (primary hemorrhage) while at the hospital due to surgical reasons (surgical site bleed that required suturing). Eight patients had delayed postoperative bleeds, after being discharged (due to eating hard food/Trauma). Only total of four patients had major bleeds, requiring surgical intervention. Conclusion: Despite guidelines recommending not doing coagulation testing prior to surgeries, many local surgeons still consider preoperative coagulation testing as a standard practice to evaluate the patients bleeding risk prior to any surgical procedure. This has resulted in unnecessary delays in surgeries (reaching up to a year in many patients) besides the parents/patients anxiety and additional total cost. We recommend awareness campaigns for surgeons and adhering to guidelines of taking detailed hemostatic history. Reference: Chee YL1, Crawford JC, Watson HG, Greaves M. Guidelines on the assessment of bleeding risk prior to surgery or invasive procedures. British Committee for Standards in Haematology. Br J Haematol. 2008 Mar;140(5):496-504. Keywords: Coagulation testing, Bleeding History, Surgery Disclosures No relevant conflicts of interest to declare.

Introduction: Mutations in the epigenetic regulators are commonly found in myeloid disorders including Myeloproliferative Neoplasm (MPN). Primary myelofibrosis, dysplastic changes and severity of the disease were associated with the mutation load. Most of the studies had a limited number of targeted genes and included a mixture of JAK2 positive and negative disease. The objective of this study is to assess the impact of mutations in the epigenetic regulators on the presentation of patients with JAK2 V617F positive MPN. Methods: We retrieved the clinical and laboratory information on 61 consecutive eligible patients. Mutation analysis of the entire coding regions of ASXL1, ASXL2, CBL, CEBPA, CSF3R, DNMT3A, EZH2, IDH2, TET1 and TET2 genes was performed using next generation sequencing (NGS; Ion PGM Sequencer; Thermo Fisher ScientificÒ). The library was constructed and the templates were prepared using the PGM tool. The variants were annotated using the ClinVar database and the prediction from the Scale-Invariant Feature Transform (SIFT) and or Polymorphism Phenotyping (Polyphen) algorithms. Alignment, variant filtering and annotation were performed using Ion Torrent Suite. Standard descriptive and analytical statistics were used as appropriate to describe and compare different groups. The MPN subtype, bleeding, thrombosis, hemoglobin, platelet count, White Cell Count (WBC), Lactate Dehydrogenase (LDH) and erythropoietin level were compared for each candidate variant. An alpha threshold of 0.05 was used with no adjustment for multiple comparisons as the analyses were considered exploratory. All statistics were performed using R program. Variants were selected for further experimentation based on their frequency and association with the clinical information at diagnosis. Results: Sixty-one patients were included (Polycythemia Vera: 29, Essential Thrombocythemia: 21, Primary Myelofibrosis: 9, MPN unclassifiable: 2) with a median age of 62 years (Interquartile Range [IQR]: 44 - 70). Male to female ratio was 35:26. The median hemoglobin, WBC, platelet count, LDH and erythropoietin were 14.6 g/dL (IQR: 12.8 - 16.8), 11.5 *109/L (IQR: 11.5 - 14.4), 507 *109/L (IQR: 391 - 779), 265 mU/mL (IQR: 231 - 409) and 1.2 mU/mL (IQR: 1.0 - 4.8) respectively. At presentation, 54% had splenomegaly, 23% had an arterial or venous thrombosis, and 5% had bleeding. Sixty-three variants were found in the samples tested. The median mutation load was 13 variants (Range: 11-14). Patients with higher than the median mutation load had higher mean erythropoietin (7.8 vs. 0.9 g/dL; p = 0.02016). ASXL1 p.Leu815Pro variant was found in all patients. Only three variants were found in the ClinVar database. Seven variants were predicted to be pathogenic (ASXL1: 1, EZH2: 1, IHD1: 1, TET1: 1 and TET2: 3). Patients with TET2: p.Leu1721Trp variant had 6.4 higher odds of bleeding (p = 0.04345). Patients with TET2: p.His1778Arg variant had a lower WBC (9.1 vs. 13.9 *109/L; p = 0.01699) and LDH (213 vs. 348 mU/mL; p = 0.0006528) while those with TET1: p.Lle1123Met variant had a higher WBC (13.5 vs. 8.3 *109/L; p = 0.02756). None of the remaining comparisons were statistically significant. Conclusions: Incorporation of clinical information facilitates the prioritization of variants from DNA sequencing experiments. In MPN, we recommend ASXL1: p.Leu815Pro (expressed in all patients), TET2: p.Leu1721Trp (associated with bleeding), TET2: p.His1778Arg (correlated with the WBC and LDH) and TET1: p.Lle1123Met (correlated with LDH) for further functional experimentation. Disclosures No relevant conflicts of interest to declare.

Objectives: Hemoglobin A2 (HbA2) is elevated in the presence of beta thalassemia trait and it is used as an indicator of its presence. High-Performance Liquid Chromatography (HPLC) overestimates HbA2 in patients with Sickle Cell Disease (SCD) due to the co-elution of HbS in HbA2 column. The optimal cut-off level of HbA2 to indicate the presence of beta thalassemia trait has not been well established in patients with SCD. We aim to define the optimal cut-off level of HbA2 to differentiate between SS and S/Beta SCD genotype variants. Methods: In this cross-sectional study, we included 241 patients with SCD who have either SS or S/Beta genotype based on their HPLC and the Sickledex test®. The diagnoses were confirmed by the direct sequencing of PCR amplified products of all exons, exon-intron junctions and promoter region of the beta globin gene. We retrieved the following clinical and laboratory variables from the electronic health records: age, gender, Hemoglobin (Hb), Mean Corpuscular Volume (MCV), Red Blood Cell (RBC) count and HbA2. We used the receiver operating curve (ROC) analysis to obtain the optimal cut-off level of HbA2 using the maximum sensitivity and specificity (Youden criteria). All descriptive and analytical statistics were performed using R program. The ROC analysis was performed with the "OptimalCutpoints" package available in R program. Results: Among the 241 patients included in the analysis, SS and S/Bthal patients were 81% and 19% respectively. Male to female ratio was 126:115. Fifty-two percent were using hydroxyurea. The median HbA2 level was 4.5% (Range: 0.0-6.5) in the SS group and 6.5% (Range: 3.5-8.2) in the S/Bthal group. The median Hb, MCV and RBC count was 9.4 g/dL (Range: 5.3 - 15.0), 75 fL (55 - 111) and 3.8 *1012/L (1.9 - 6.3) respectively for the SS group; while it was 9.7 g/dL (6.6 - 12.3), 68 fL (57 - 86) and 4.2 *1012/L (2.5 - 5.4) respectively for the S/Bthal group. The optimal cut-off level for HbA2 was estimated to be 5.7% using a sensitivity of 91% and a specificity of 92%. The positive and negative predictive values were 75% and 98% respectively. The discrimination estimated using the Area Under the Curve (AUC) was 0.936 (95% Confidence Interval: 0.878-0.994). Conclusions: The optimal cut-off HbA2 level to differentiate SCD with the S/Bthal genotype from the SS genotype is 5.7% with a high sensitivity, specificity and discrimination. The unexpected overlap in the MCV and the RBC count is likely related to the high rate of Alpha thalassemia trait in the analyzed population. Incorporation of the presence of alpha thalassemia trait in the analysis may improve the discrimination of MCV and RBC count. Disclosures No relevant conflicts of interest to declare.

Background and Objectives Hodgkin's lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. The clinical presentation and survival rate of these patients have not been described in Oman. We, therefore, aimed to describe the clinical characteristics and survival rate of patients with classical Hodgkin's lymphoma. Methods This is a retrospective study that was conducted in a tertiary care centers in the Sultanate of Oman. All Omani adults with histopathological confirmed diagnosis of classical Hodgkin's lymphoma from 2000 to 2016 were included in this study. The demographic, clinical, and survival rate were recorded and analyzed. Results A total of 273 patients (45 % females and 55% males, mean age 32) fulfilled the inclusion criteria with histopathological confirmed diagnosis of classical Hodgkin's lymphoma. The commonest presenting feature was lymph node enlargement (83%); followed by fever (48%). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (71%). The most common stage was II 34%. The most common chemotherapy regimen used as the first line was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (89%). Five and 10-year survival rates were 93.8 % and 99.2%, respectively. Conclusions This is the first study that demonstrates the demographic, clinical and survival rate of HL patients in Oman, and provides a general picture of the HL patients in our country. Disclosures No relevant conflicts of interest to declare.

Background The management of pregnant women with anti-Jsb is challenging due to the paucity of antigen-negative blood for fetal and neonatal transfusion. Case Report A 29-year-old woman with anti-Jsb was referred for assessment of recurrent fetal losses. With the presence of the sister as a historically matched donor, she was planned for active surveillance for fetal anemia during pregnancy. Study Design and Methods The fetus remained well until 21 weeks of gestation when signs of fetal anemia and early hydrops fetalis were noted. Anti-Jsb titer was at 128. The sister's red blood cells (RBCs) were cross-match incompatible. Urgent intrauterine transfusion (IUT) was performed with washed irradiated maternal RBCs, donated after cessation of heparin. The mother was given intravenous iron (IV-Fe) and continued on weekly recombinant human erythropoietin (rHu-EPO). Results Repeated IUTs were needed every 1 to 3 weeks. Throughout a 7-week period, three maternal donations were performed with total donated whole blood volume of 1250 mL, supporting four IUTs. At 29 weeks of gestation, the procedure was complicated by umbilical cord hematoma necessitating urgent cesarean section. A male newborn was delivered, transfused at birth, and subsequently treated with phototherapy and five top-up transfusions. Conclusion This case represents a successful example of managing hemolytic disease of the fetus due to a rare antibody using maternal blood. It also supports previous data on safety of maternal donations during pregnancy and the use of combination of rHu-EPO and IV-Fe as a supportive measure.

Prognostic studies of T-cell lymphoblastic leukemia/lymphoma (T-ALL) have been performed in small patient cohorts with conflicting results. We systematically reviewed 67 adult T-ALL patients diagnosed and treated at our institute to identify clinical and pathologic prognostic factors. The median initial WBC was 21.3 × 109/l. Blasts expressed at least one myeloid-associated antigen in 33%. Karyotypes were abnormal in 32% of the cases. Fifty-six of 64 patients (88%) achieved complete remission (CR). In univariate analysis, age, gender, initial WBC, CD10, CD34 and abnormal karyotype did not predict CR. Patients expressing at least one myeloid-associated antigen had a CR of 74% compared to 94% (p = 0.04) for those not expressing myeloid antigens. None of the above factors affected relapse-free or overall survival in this cohort. Our study indicates that expression of myeloid-associated antigens is associated with a lower CR rate in adult T-ALL and may be considered in risk stratification for induction chemotherapy.

High WBC plays a major role in the pathogenesis of many of the complications seen in patients with sickle cell disease (SCD).1 Individuals with Sickle cell trait may develop SCD-related complications in conditions of severe stress.2 G-CSF increases the WBC and may contribute to some of the complications in individuals with sickle cell trait when used in stem cell mobilization. To the best of our knowledge, only one small study3 assessed the safety of the mobilization of stem cells in individuals with sickle cell trait. Herein, we aimed to compare mobilization adverse events between donors with and without sickle cell trait.

Although patients homozygous for the sickle cell disease (SCD) mutation have an identical genotype, the severity of the disease can be extremely variable. The hemoglobin (Hb) S mutation has been associated with five different beta S-globin gene cluster haplotypes (βS-haplotypes) that show different clinical expression. Because genetic modifiers can modulate treatment response, we hypothesized that βS-haplotypes can affect levels of invariant natural killer T (iNKT) cells, which are known to play a key role in the pathogenesis of SCD, and are being considered as a potential target to treat acute crises in SCD patients. Herein we evaluated the impact of βS-haplotypes and HbF concentration on iNKT cell and dendritic cell (DC) subsets in a well-defined group of patients with SCD in a steady state. Sickle cell anemia patients were selected based on the history of patients, clinical examination and hematological findings. The βS-haplotypes were identified by polymerase chain reaction-restriction fragment length polymorphism analysis for seven restriction sites. The iNKT cell subsets were characterized by the positive-staining of Vα24Jα18 T cell receptor alpha chain, along with CD3, CD4 and CD8 surface markers and the intra-cellular cytokine production of interferon-gamma (Th1-like), interleukin-4 (Th2-like) and interleukin-17 (Th17-like) cells using flow cytometry and cell culture. The myeloid DC (mDC) and plasmacytoid DC (pDC) cells were identified by the expression of HLA-DR, CD123, CD11c, Lin and CD1d, a non-classical molecule that induces the activation of iNKT cells by flow cytometry. Comparisons among βS-haplotypes were performed using ANOVA and unpaired t test, while the Spearman's correlation was used to assess associations. Among the 125 sickle cell anemia patients studied, Benin haplotype (40%) was the most common followed by Bantu (21%), Arab/Indian (18%), Atypical (12%) and Benin/Bantu or Benin/Arab-Indian or Bantu/Arab-Indian (9%). The majority of subjects with Benin/Benin βS-haplotype had a severe to moderate clinical profile similar to Bantu/Bantu or Arab/Indian βS-haplotype groups (P=0.23). A trend toward increased levels of CD3iNKT, CD4iNKT and CD8iNKT cell subsets was observed in the subjects with the Benin/Benin βS-haplotype, when compared to other βS-haplotype groups (P=0.06). Interestingly, subjects with the Benin/Benin βS-haplotype exhibited slightly higher levels of Th1-like cells, but not Th2-like and Th17-like cells, when compared to subjects with the Bantu/Bantu or Arab/Indian βS-haplotype groups (P=0.047). Comparisons between the levels of mDC and pDC cell subsets, as well as the expression of CD1d on these DC cells, showed no statistically significant differences among the βS-haplotype groups (P=0.42). Similarly, levels of iNKT cell subsets, Th1-like, Th2-like, and Th17-like cells as well as DC subsets were similar among patients who received or not hydroxyurea therapy, independently of βS-haplotype groups (P= 0.09). Likewise, coexistence of high HbF and βS-haplotypes did not show any significant association with iNKT cell subsets. Collectively, our findings suggest that neither the βS-haplotypes or HbF levels nor the hydroxyurea therapy or clinical severity appeared to be associated with iNKT cell or DC cell subsets in patients with SCD. The effects of other genetic modifiers such as alpha/beta-thalassemia and G6PD deficiency on iNKT cell subsets need to be evaluated in future studies. Disclosures No relevant conflicts of interest to declare.

Recent observational cohort studies indicated that the incidence of connective tissue diseases such as systemic lupus erythematous (SLE), in adult patients with sickle cell disease (SCD), appears to be increasing. The exact causes underlying this increased risk are still unknown, but patients with SCD are at risk of infections due to immune dysfunction, and a link with regulatory B (Breg) cells is possible as these cells suppress inflammatory responses, maintain tolerance and prevent the development of SLE in animal models via the production of interleukin-10 (IL-10). Herein, we numerically and functionally evaluated Breg cells in a well-defined group of SCD patients. The classification for SCD was based on patients' history, clinical examination, hematological and radiological findings. The American College of Rheumatology (ACR) criteria were used to classify and diagnose SLE patients with or without SCD. Patients were stratified into three groups including SCD patients with SLE (n=21), patients with SCD only (n=24) and patients with SLE only (n=24). Normal healthy individuals (n=24) were used as controls. Circulating levels of Breg cells were prospectively assessed by immuno-phenotyping using specific surface markers, CD19, CD24 and CD38 by flow cytometry. The functional properties were evaluated by IL-10 production and STAT3 phosphorylation after stimulation and cell culture. Unstained cells and n-1 monoclonal antibodies along with live and dead stain were used as controls in all experiments. Comparisons among study groups were performed using ANOVA and unpaired t test, while the Spearman's correlation was used to assess associations. The demographic data were similar among the study groups. All participants were free of infections such as human immunodeficiency virus, hepatitis B and C virus and syphilis. SCD patients with SLE and patients with SLE only were positive for autoimmune markers and showed an average ACR score of five and six respectively. The frequency of Breg cells, as phenotypically defined as CD19+CD24hiCD38hi, ranged between 1.5-8% in healthy controls. The circulating levels of Breg cells were significantly reduced in SCD patients with or without SLE and patients with SLE only when compared to the healthy controls (p Disclosures No relevant conflicts of interest to declare.

Introduction and Objectives: Patients with Thalassemia Major (TM) develop various complications related to iron overload and transfusion associated infections. It is unknown as yet if the specific genotype leading to TM has further impact on the development of liver fibrosis. Therefore, we planned to assess the impact of genotypes in patients with TM on the risk of liver fibrosis. Methods: We included 88 patients with TM with available genotyping data in this study. These patients were followed and transfused in a single tertiary academic center. All those patients had their liver fibrosis assessed by ultrasound elastography (FibroScan device) with a cut off value of 7.8 kPa. The genotyping was done using Amplification Refractory Mutation System (ARMS)-hot start-polymerase chain reaction (PCR) technique. Iron overload was assessed using the average serum ferritin in the 5 years prior to the liver fibrosis assessment. Association was assessed using Chi-squared test and adjustment using multivariable logistic regression. Results: A total of 88 patients were included with a median age of 27 years (Interquartile range [IQR]: 23-31). Females constituted 54% of patients and 34% of patients were splenectomised. The median alanine transaminase, aspartate transaminase, albumin and total bilirubin were 31 U/L (IQR: 20-58), 30 U/L (IQR: 18-46), 46 g/L (IQR: 43-48) and 23 µmol/L (IQR: 15-34) respectively. The median ferritin and liver iron concentration assessed by MRI T2* were 1472 µg/L (IQR: 741-2760) and 7.0 mg/gdw (IQR: 3.5-15.9) respectively. Thirty seven percent of patients had positive serology for HCV while 1% of patients had positive serology for HBV. The genotypes seen in this study included homozygous IVS-I, 5 (G-C) in 39 patients, homozygous codon 44 (-C) in 19 patients, double heterozygous IVS-I, 5 (G-C)/25 bp deletion in 5 patients and others (≤ 3 patients each) in 25 patients. The proportion of patients with fibrosis was 55%. The proportion of patients with fibrosis in the homozygous IVS-I, 5 (G-C) group was 58% compared to 52% in all other genotypes and the difference was not statistically significant (odds ratio of 1.3 with a p value of 0.6652). The impact of the genotype remained non-significant after adjustment of iron overload in the multivariable logistic regression model. The only statistically significant factor was the iron overload (p values: iron overload 0.006, genotype 0.966). Conclusion: The risk of liver fibrosis is associated with the iron overload in patients with TM. There is no additional independent impact of the genotype. Further studies with larger sample size to study the impact of various genotypes are required to confirm these results. Disclosures No relevant conflicts of interest to declare.

Introduction and Objectives: Iron overload in patients with Thalassemia Major (TM) leads to various complications including liver fibrosis. The independent impact of gender on this risk has been previously investigated but not yet confirmed. We, therefore, planned to assess the independent impact of gender in patients with TM on the risk of liver fibrosis. Methods: We included 96 patients with TM followed and transfused in one academic tertiary hospital. Patients underwent assessment of liver fibrosis using ultrasound elastography (FibroScan device) with a cut off value of 7.8 kPa. The mean ferritin in the 5 years prior to elastography assessment was used to represent iron overload. Association was tested using Chi-squared and the independent impact of gender was confirmed in the multivariable logistic regression with a model that included mean ferritin and gender. Results: The median age of the 96 included patients was 26 years (Interquartile range [IQR]: 22-30). Males constituted 45% of patients and 33% of patients were splenectomised. The median alanine transaminase, aspartate transaminase, albumin and total bilirubin were 30 U/L (IQR: 18-64), 30 U/L (IQR: 18-46), 46 g/L (IQR: 44-48) and 21 µmol/L (IQR: 14-32) respectively. The median ferritin and liver iron concentration assessed by MRI T2* were 1293 µg/L (IQR: 753-2715) and 6.7 mg/gdw (IQR: 3.5-16.1) respectively. Thirty seven percent of patients had positive serology for HCV while 1% of patients had positive serology for HBV. The proportion of patients with fibrosis as assessed by elastography was 59%. The proportion of male patients with fibrosis was 70% compared to 51% in female patients with a trend towards statistical significance (odds ratio [OR] of 2.2 with a p value of 0.094). In the multivariable logistic regression model, both gender (OR of 3.0, P value of 0.0188) and ferritin (OR of 1.0004, p value of 0.0036) were statistically significant independent predictors of liver fibrosis. Conclusion: Male gender increases the risk of liver fibrosis independent from iron overload. Our study confirms the previously suspected but unproven association. Follow up and therapy may be tailored to include gender as a decision factor. Larger studies are needed to further confirm these results. Disclosures No relevant conflicts of interest to declare.

Introduction and Objectives: Iron chelators are effective in reducing iron burden and in improving clinical outcomes in patients with transfusional iron overload. However, limited data are available on their efficacy and safety in transfusion-dependent patients with low iron overload, due mainly to concerns of chelation toxicity observed with deferoxamine (DFO) in patients with serum ferritin (SF) < 1500ug/L. Deferiprone (DFP) has markedly lower affinity for iron (pFe3+ log stability constant = 19.9) than that of deferoxamine (26.6), and may provide a better safety profile in patients with low iron overload. The objective of this study is to evaluate the safety and efficacy of DFP in patients with thalassemia major (TM) and SF Methods: A total of 32 patients with TM (15 males) who had achieved SF Results: Patients were followed for a median of 4.5 years (Range: 1-11 years). The median age at time of switch was 22.7 years (Range 11-28). The mean packed red blood cell volume transfused during the study was 197 mL/kg/year (Range: 157-282 mL). There was no significant increase in the SF (Baseline 392 ug/L; Last assessment 418 ug/L; p value 0.55) or the liver iron concentration (Baseline 3.44 mg/g dw; Last assessment 3.1 mg/g dw; p value 0.54) during the follow up. On the contrary, there was a statistically significant improvement in the cardiac T2* (Baseline 30 ms; Last assessment 38 ms; p Conclusion: Long-term DFP therapy in patients with TM and low iron overload was effective in stabilizing SF and LIC and was associated with improvement in the myocardial iron. The safety profile was consistent with those observed during therapy in patients with more severe iron burden and there were no increase in the unexpected adverse drug reactions. Disclosures No relevant conflicts of interest to declare.

[Figure][1] A 34-year-old man from India presented with a 1-month history of intermittent high-grade fevers, generalized weakness, and cough. The patient had a history of being treated for malaria. He was lethargic but vitally stable. Complete blood count showed thrombocytopenia with a

Recent data suggests that invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes that express markers characteristic of both T cells and natural killer cells, play a pivotal role in the pathogenesis of sickle cell disease (SCD). Indeed, these cells are being considered as a potential target to prevent or treat acute crises of SCD in adult patients. However, the phenotypic and functional characteristics of circulating iNKT cell subsets in children with SCD remain unknown. Herein, we functionally evaluated iNKT cell subsets in relation to myeloid dendritic (mDC) and plasmacytoid dendritic (pDC) cells and markers of SCD severity in well-defined groups of children with SCD. The classification criteria for SCD was based on the history of patients, clinical examination, hematological and radiological findings. Blood iNKT cell subsets were prospectively studied in 68 children with SCD and normal controls using peripheral blood mononuclear cells, 10-color flow cytometry and culture assays. The iNKT cell subsets were identified by the positive-staining of Vα24Jα18 T cell receptor alpha chain, along with CD3, CD4 and CD8 surface markers and the intra-cellular cytokine production of interferon-gamma (Th1-like), interleukin-4 (Th2-like) and interleukin-17 (Th17-like) cells. The mDC and pDC cells were phenotypically characterized by the expression of HLA-DR, CD123, CD11c, Lin and CD1d, a non-classical molecule that induces the activation of iNKT cells. SCD patients were stratified into three groups including surgically splenectomized (n=23), large spleen (n=21) and steady state (n=24). Comparisons among study groups were performed using ANOVA and unpaired t test, while the Spearman's correlation was used to assess associations. Compared to normal individuals, splenectomized and steady state subjects, large spleen patients exhibited significantly higher levels of CD3iNKT, CD4iNKT and CD8iNKT cells (P=0.04). There were no differences in the levels of iNKT cell subsets between splenectomized and steady state subjects (P=0.56). The levels of mDC and pDC cells were also similar among the study groups (P=0.70). Interestingly, the large spleen patients tend to have higher CD4, but not CD8, Th1-like, Th2-like and Th17-like iNKT cells compared to splenectomized and steady state subjects (p=0.08). The expression levels of CD1d on both mDC and pDC were equivalent among study groups. The levels of CD3iNKT cells were negatively associated with baseline haemoglobin F levels (r=0.45, P=0.04) but not with age, time since splenectomy, spleen size or total hemoglobin levels at phlebotomy. Collectively, these results further advance the functional characterization of circulating iNKT cell subsets in children with SCD and reveal that surgically splenectomized patients have preserved function of iNKT cell subsets that are to be considered for clinical purposes. Disclosures No relevant conflicts of interest to declare.

Congenital atransferrinemia is an extremely rare hematologic disease caused by transferrin deficiency, and characterized by microcytic hypochromic anemia with iron overload, and that can be fatal if left untreated. The prevalence is unknown. To date, there have been 16 reported cases from 14 families, with few cases confirmed genetically. Here, we report a new case from the Middle East that was diagnosed on clinical ground, and then confirmed by genetic testing through international collaboration. M.T is a 32 months old Egyptian boy, 2nd child of a consanguineous couple, with a healthy 5.5 years older sister. He was born at full term by SVD, suffered physiological jaundice as a newborn. He also had Talipes equinovarus and hypospadias. He was first brought to medical attention at a local hospital at the age of 8 months because of a febrile illness, when he was accidentally discovered to be very pale with Hb of 4.8 g/dl. He received packed RBC transfusion followed by oral iron therapy for 2 weeks, and then another assessment revealed Hb 6.9 g/dl, so he received another transfusion, and then referred to the University Hospital for further assessment. Examined at the age of 20 months, he had marked pallor, tachycardia, and mild hepatosplenomegaly, otherwise the child was normal with average anthropometric measurements. CBC revealed severe microcytic hypochromic anemia (Hb 4.8, MCV 54 fl, MCH 18 pg), MCHC 30 g/dl). Hb electrophoresis: normal Screening for Alfa and Beta thalassemia: normal wild type. Iron profile revealed hypoferremia (Serum iron: 6 ug/dl), TIBC: below assay range, and high serum ferritin: 669 ng/ml. Based on these results, atransferrinemia was suspected, so he was tested for serum transferrin, and reported as very low (8 mg/dl). Bone marrow aspirate was normocellular for age, showing normal granulopoiesis, normoblastic erythropoiesis, and normal megakaryopoiesis, no evidence of dysplasia or abnormal or malignant cells. Prussian blue stain showed depleted iron stores. Serum lead, bilirubin, liver and kidney function tests were normal Both parents had normal blood picture and iron profile. Human apotransferrin was not available in Egypt, so, plasma transfusion was instituted every 2-4 weeks, through which regimen he is maintaining Hb level between 7-12 gm/dl. As molecular diagnosis for that very rare disease was not feasible in Egypt, after parental consent, blood samples from patient and both parents were sent to Dr. von Haunersches Kinderspital, Munich, and a novel transferrin genemutation was detected by NGS(TF, NM_001063.3, c.1247A>G, p.Y416C) that is currently being validated by Sanger sequencing. To the best of our knowledge, this is the first atransferrinemia report from the Middle East, where prevalence of thalassaemia and iron deficiency anemia is high. However, this rare anemia case underlines the importance of considering rare hereditary disorders like atransferrinemia as the cause for unexplained hypochromic microcytic anemia associated with iron overload, in order to initiate appropriate treatment and avoid iron overload related complications. Disclosures No relevant conflicts of interest to declare.

Birth is not only considered the first hemostatic challenge for a child with hemophilia A, but also it can result in one of the most devastating and often preventable type of bleeding in hemophilic newborns. Three to four percent of infants with hemophilia experience a head bleed at delivery. The optimal mode of delivery of the hemophilic carrier expecting an affected child is still a matter of uncertainty and debate. The aim of this study was to evaluate the frequency of major bleeding in the neonatal period and to examine the association between mode of delivery and neonatal intracranial hemorrhage (ICH) in an Arab cohort of infants with hemophilia A. Subjects and methods: A retrospective multi-center study of children with severe hemophilia A (age 0-18 years) was conducted. Five hemophilia treatment centers distributed across four Arabian Gulf countries participated in the study. Two centers from Oman and one center of each of KSA, UAE and Kuwait were included. The collected data were date of birth, maternal parity, mode of delivery, duration of labor, admission to neonatal intensive care unit, symptomatic ICH, and other bleeding episodes. Review of electronic patient record along with telephone interviews when needed were the tools used for data collection. Results: A total of 153 patients were found. Most of them were born through spontaneous vaginal delivery (SVD) (125 patients; 82 %). Vacuum extraction was adopted in six patients (4%), while twenty two patients were offered caesarian section (CS) (14%). ICH was reported in a total of four patients (2.6%). All of them were full term babies with variable time interval between the onset of the bleed and birth. One patient presented at birth, another presented at the age of 4 weeks while the remaining two had the bleed at the age of 2 weeks. Vacuum extraction was associated with the highest risk of ICH (two patients; 33 %).The other two patients were born by SVD (1.6 %). CS was not associated with ICH. Conclusions: Normal vaginal delivery is still considered a safe journey through the birth canal for hemophilic newborns. Larger prospective studies are needed to define an evidence-based optimal mode of delivery for the hemophilia carrier expecting an affected child. Disclosures No relevant conflicts of interest to declare.

Background: Iron overload is a leading cause of morbidity and mortality in beta thalassemia and chelation therapy remains the mainstay in reducing iron burden. For effective chelation, optimal drug dosage with close monitoring of side effects is crucial. The safety and efficacy of deferasirox has been extensively studied in adult population. We aimed at evaluating the liver enzyme changes and safety profile of deferasirox in pediatric patients with thalassemia major. Materials and Methods: A retrospective study of 30 patients (range 2-15 years) with thalassemia major on regular follow up at the Pediatric Day care Center, Sultan Qaboos University Hospital was performed to evaluate the side effects of deferasirox over a mean of 15 month follow-up period. Data from electronic patients' records was collected for age, gender, serum ferritin, alanine transaminase, (ALT), aspartate transaminase (AST), dose and side effects of deferasirox. Data were analyzed using SPSS software version 19. Results: Thirteen (44.8 %) patients had either ALT or AST elevation above 2 times upper limit of normal (ULN). Except for two (6.8%) patients with enzyme elevations more than 5 times ULN, the majority of patients had mild transaminitis. None of the patients had liver enzyme elevation above 10 times ULN. The other side effects included fever (17.24%), nausea and vomiting (10.34% each), diarrhoea (13.79%), skin rash (21.4%), elevated serum creatinine with either 2 consecutive readings more than 33% of baseline level and/or single reading above 60% baseline (17.24%). The mean serum ferritin dropped from initial baseline level of 1236.21 ± 354 ng/ml (Range 534 -2821 ng/ml) to a level of 950 ± 320 ng/ml (Range 550-1900 ng/ml) at the end of the study period; with a mean deferasirox dose of 32.72 ± 4.79 mg/kg/day. Conclusion: Majority of our patients had mild transaminitis not requiring dose modification or interruption of chelation. Patients with significant elevations of liver enzymes more than 5 times ULN showed prompt recovery of transaminitis within 4-5 weeks of dose reduction of deferasirox by 5 mg/kg/day and future dose increments were well tolerated. Except for significant elevations in serum creatinine requiring dose reduction or short interruption, the other adverse events were well tolerated and did not warrant dose modification. Deferasirox was effective in reducing serum ferritin levels and was well tolerated in our young patients with thalassemia major. Table 1 PatientCharacteristics Numberof patients, n 30 Meanage of patients, years Range,years 7.24± 3.4 2-15 Meanserum ferritin, ng/ml Range,ng/ml 1236.21± 354 534-2821 Meandose of deferasirox (mg/kg/day) 32.72± 4.79 Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Background & Purpose Pulmonary hypertension (PH) in sickle cell disease (SCD) is an important risk factor for complications including sudden death. In this study, we aimed to determine the prevalence of PH and correlate the echocardiographic parameters and general laboratory data with markers of hemolysis and serum NT pro-brain natriuretic peptide [BNP] concentrations in Omani SCD patients. Methods A cohort of 163 SCD patients [Mean age 25.4±8.4 years], in steady state was prospectively screened for PH with Doppler echocardiography (defined as a tricuspid regurgitation jet flow velocity of ≥ 2.5 m/sec and/or mean pulmonary artery pressure [mPAP] ≥25 mmHg). After a written informed consent, all patients were investigated with a complete blood count, renal chemistry, hemolytic parameters including LDH, haptoglobin, liver function tests, coagulation studies, HPLC studies including HbS and HbF level estimations, X ray Chest, ECG, ABG, Pulmonary function tests, Pulse oximetry, and Serum NT pro-BNP levels. Results In the evaluable patient cohort of 116 subjects [63 females, 53-males], the prevalence of PH was 5.2%. No statistically significant differences were detected in Hb levels, ECG, chest radiography, pulmonary function tests between patients with and without PH. However, plasma NT pro-BNP levels were significantly correlated with PAH [r=0.934, p Conclusions Serum NT pro-BNP is a strong indicator of PH in SCD patients. Doppler ultrasound echocardiography is a useful initial screen for PH in SCD patients. The correlation between PH and hemolytic markers suggests an implication in the pathogenesis of PH. Disclosures: No relevant conflicts of interest to declare.

Abstract 2280 Introduction: Pre-donation screening of blood donors are currently based on venous or capillary blood sampling. Adoption of a non-invasive hemoglobin estimation may increase blood donor recruitment. Masimo Pronto-7 Pulse CO-oximetry device is a spectrophotometry based device used to estimate the hemoglobin (Hb) level non-invasively, waiving the need of blood sampling. It has not been validated in normal blood donors. The primary objective of our study was to validate the pulse CO-oximetry based hemoglobin estimation in normal blood donors. Methods: We conducted a prospective observational study on 106 whole blood donors attending the blood bank of a tertiary care center over 4 weeks. We estimated a Spot Hemoglobin (Sp Hb) concentration using Masimo Pronto-7 Pulse CO-oximetry device (two measurements per donor) and compared it to a venous sample Hb (Reference Hemoglobin; Ref Hb) measured using Abbott CELL-DYN Sapphire hematology analyzer. We calculated Pearson correlation coefficient and coefficient of determination (R2). The multivariable linear regression model of predicting the estimation differences included age, gender, weight, height, blood pressure and reference hemoglobin. Results: We enrolled 106 donors (98 males, 8 females) with a mean age of 27 years (SD 6.2; 18–49) and a mean Ref Hb of 14.2 g/dL (SD 1.2; 11.5–17). The mean Sp Hb was 14.4 g/dL (SD 1.2; 11.3–16.7). The correlation coefficient between the Sp Hb and Ref Hb was 0.46 (R2 = 21%) with a mean difference of 0.2 g/dL (SD 1.2; −4.5 to 3). In the multivariable model, height (p =0.015) and Ref Hb level (p Conclusions: Our study demonstrated the validity of the CO-oximetry Hb measurement in normal blood donors and with good reproducibility. Larger prospective studies are needed to confirm our findings. Disclosures: No relevant conflicts of interest to declare.

Abstract 5179 Introduction: Patients with β-thalassemia major receive regular blood transfusions. Non-invasive hemoglobin (Hb) estimation may simplify their care. Masimo Pronto-7 Pulse CO-oximetry device is used to non-invasively estimate the hemoglobin level but has not been previously validated in this group of patients. The primary objective of this study was to validate the pulse CO-oximetry based hemoglobin estimation in children and adults with thalassemia major. Methods: We conducted a prospective observational study on 108 children and adults with thalassemia major attending the daycare thalassemia center of a tertiary care hospital over 6 weeks. We estimated a spot Hemoglobin (Sp Hb) level using Masimo Pronto-7 Pulse CO-oximetry device (two measurements per patient) and compared it to a venous sample Hb (Reference Hemoglobin; Ref Hb) measured using Abbott CELL-DYN Sapphire hematology analyzer. We calculated Pearson correlation coefficient and coefficient of determination (R2). The multivariable linear regression model of predicting the estimation differences included age, gender, weight, height, blood pressure and reference hemoglobin. Results: We enrolled 108 patients (54 males, 54 females) with a mean age of 21. 6 years (SD 7. 3; 2. 5–38). There were 156 estimation episodes. The mean Ref Hb and SpHb were 9. 4 g/dL (SD 0. 9; 7. 1–12. 3) and 11. 1 g/dL (SD 1. 2; 7. 5–14. 7) respectively. The correlation coefficient between the Sp Hb and Ref Hb was 0. 49 (R2 = 24%) with a mean difference of 1. 7 g/dL (SD 1. 1; −1. 2 to 4. 3). In the multivariable model, Ref Hb level was the only statistically significant predictor of the difference in measurement (p =0. 002). There was a strong correlation between the two CO-oximetry Hb measurements (correlation coefficient 0. 70, R2 = 50%). Conclusions: Our results indicate that Masimo Pronto-7 Pulse CO-oximetry device overestimates the hemoglobin level and it cannot be recommended for patients with thalassemia major. Larger prospective studies are needed to confirm these results. Disclosures: No relevant conflicts of interest to declare.

Abstract 4770 Introduction: The care of patients with Sickle Cell Disease (SCD) is frequently complicated by difficult venous access complicating blood sampling for laboratory investigations including hemoglobin (Hb) measurement. Non-invasive hemoglobin concentration monitoring is a potential solution, albeit not validated yet in patients with SCD. The primary objective of this study was to validate non-invasive pulse CO-oximetry based hemoglobin estimation in this patient population. Methods: We conducted a prospective observational study on patients with SCD admitted to the inpatient wards over 4 weeks in a tertiary care hospital. We estimated a spot Hemoglobin (Sp Hb) measurement using Masimo Pronto-7 Pulse CO-oximetry device (two measurements per patient) and compared it to a venous sample Hb (Reference Hemoglobin; Ref Hb) measured using Abbott CELL-DYN Sapphire hematology analyzer. We calculated Pearson correlation coefficient and coefficient of determination (R2). The multivariable linear regression model of predicting the estimation differences included age, gender, weight, height, blood pressure and reference hemoglobin. Results: We enrolled 98 patients (45 males, 53 females) with a mean age of 26 years (SD 8.8; 14–75) and a mean Ref Hb of 9.2 g/dL (SD 1.5; 5.3–13). The mean Sp Hb was 10.1 g/dL (SD 2.0; 5.3–14.5). The correlation coefficient between the Sp Hb and Ref Hb was 0.54 (R2 = 29%) with a mean difference of 0.9 g/dL (SD 1.7; −4.8 to 4.5). In the multivariable model, gender (p =0.042) and Ref Hb level (p=0.001) were statistically significant predictors for the difference in measurement. A strong correlation between the two CO-oximetry Hb measurements was obtained (correlation coefficient = 0.81, R2 = 65%). Conclusions: Our study demonstrated the validity of the CO-oximetry Hb measurement in adult patients with SCD. Larger prospective studies are needed to confirm our results. Disclosures: No relevant conflicts of interest to declare.

Abstract 504 Background: The impact of heparin in pregnant women with previous unexplained recurrent miscarriages remains uncertain. The use of heparin in this patient population has been increasing with the hope of improving the rate of live births. We performed a systematic review of the randomized clinical trials addressing this question. Methods: We searched MEDLINE (searched July 1st 2012), CENTRAL (Issue 7 of 12, July 2012), American Society of Hematology (searched July 1st 2012), clinical trials registries (http://clinicaltrials.gov/, searched July 1st 2012), and bibliographies of relevant studies for randomized clinical trials comparing heparin (unfractionated or low molecular weight) to other best care approaches. Use of aspirin was allowed in either study arms. Included patients were pregnant women over 18 years of age with previous recurrent unexplained miscarriages (at least two at any trimester). We performed a meta-analysis using random effects models to estimate the pooled odds ratio. Statistical heterogeneity was calculated by using the I2 statistic. Results: Eight trials proved eligible, five of which provided data from 1141 patients that could be included in the meta-analysis and three of which remain unpublished. Only the subgroup of patients with no antiphospholipid antibodies or inherited thrombophilia was included. There was a total of 839 live births observed. Enoxaparin was used in four trials and nadroparin was used in one trial. All trials randomized patients before the 8th week of gestation. There were 430 live births (among a total of 561 pregnancies) and 409 live births (among a total of 580 pregnancies) in the heparin and other best care treatment arms respectively. The difference between the two treatment arms was not statistically significant with a pooled odds ratio of 1.49 (95% confidence interval: 0.84, 2.66; P = 0.17). There was a substantial heterogeneity among the results of different trials (Chi2 = 14.91, P = 0.005; I2 = 73%). Conclusions: Available evidence suggests that heparin does not increase live births in pregnant women with previous unexplained recurrent miscarriages with no evidence of antiphospholipid antibodies or inherited thrombophilia. Future trials should explore new treatment strategies. Disclosures: No relevant conflicts of interest to declare.

Abstract 3260 Background: The standard of care for patients with thalassemia intermedia (TI) is regular follow up and iron chelation therapy. Patients with TI are usually transfusion independent and receive irregular transfusion when they develop low hemoglobin levels as in case of infection. However, with the current policy, these patients are liable to many complications; thalassemic facies, growth retardation, splenomegaly, hypersplenism, hypercoagulability, pulmonary hypertension, heart failure, cholelithiasis, diabetes mellitus, hypothyroidism, osteoporosis, and hypogonadism. We planned to investigate the impact of early introduction of hypertransfusion on delaying these complications. Material and Methods: All newly diagnosed children with TI at the Pediatric Thalassemia Day Care Centre, Sultan Qaboos University Hospital, Oman, starting from August 2006 were included in the study. They were diagnosed as intermedia based on clinical grounds of late age presentation (>5 years), maintaining mean baseline hemoglobin of 7 g/dL (range 6.1–7.9 g/dL), and transfusion independence. In addition, eight patients had a definitive TI mutation Hb Dhofar [β29(GGC–GGT)gly-gly, β58(CCT–CGT)pro-arg]. They were 10 females and 10 males included in the study. The mean age at presentation was 7.17 ± 3.9 years. At diagnosis, they were started on monthly hypertransfusion program to maintain a pretransfusion hemoglobin level above 9.5 g/dl and a post transfusion level of 14 g/dl. The mean duration of transfusion therapy was 6.2 ± 3.7 years and the mean follow up duration was 7.1 ± 3.2 years. Results: None of the 20 patients developed thalassemic facies, splenomegaly or hypersplenism. Sixteen patients maintained a normal weight (above 5th centile) and height (above 10thcentile), while 4 patients were at or below the 3rd centile. Of the 10 children above eleven years of age, 7 children reached normal puberty at their expected age. All 10 patients above eleven years of age, had a normal thyroid function test (TSH 2.27 ± 1.07 mIU/L, T4 11.04 ± 2.65 pmol/L) with no clinical or laboratory evidence of diabetes. Eight of the elder patients who had echocardiography had no evidence of pulmonary hypertension. Baseline bone densitometry done in 2 patients revealed a low Z-Score (below −2.5), with no improvement on follow-up. The mean total transfusion requirement was 162 ± 23 ml/kg/year. Patients were maintained on either deferiprone (n=14, dose 87 ± 12 mg/kg/day) or deferasirox chelation (n=6, dose 32 ± 4 mg/kg/day). Preliminary results of a self esteem questionnaire of these patients were better than our older patients who had not received hypertransfusion/chelation. Conclusion: TI children who were started at presentation on hypertansfusion/chelation regimen, have improved growth, better self esteem and they did not develop many of the complications known to occur in the non-transfused ones. However, this regimen needs to be evaluated in a larger prospective cohort study and to confirm the cost-effectiveness given the regular blood transfusion and continuous iron chelation. Disclosures: No relevant conflicts of interest to declare.

Abstract 4675 Introduction: Rituximab has been used in the management of chronic immune thrombocytopenia (ITP) with promising results. The risk of losing response, however, is yet to be determined with long term follow up. Method: We retrospectively analyzed 32 consecutive patients (20 females, 12 males) with ITP (including 6 patients with secondary ITP) treated with rituximab in two tertiary care hospitals in Oman between May 2006 and May 2011. Response criteria were based on the International Consensus report (Rodeghiero F et al. Blood 2009). Result: The median age at diagnosis was 25 years (range, 4 – 58). Clinical presentation ranged from mild echymosis to more severe central nervous system bleeding. Patients received a median of one line of therapy before rituximab (range, 1–4), including 3 patients who failed splenectomy. Patients received intravenous rituximab using 375 mg/m2 once weekly for 4 weeks. The median time from diagnosis to receiving rituximab was 21 months (range, 1– 177). Only one patient was positive for Hepatitis C virus, but no hepatitis B or HIV positive in this cohort. Anti nuclear antibody was positive in 34% (10/29) of patients. The median hemoglobin and platelet counts at diagnosis were 12 g/dl (range, 5–16) and 11×109/L (range, 1–60) respectively. The median follow up time after rituximab was 26 months (95% confidence interval: 11–40). The overall cumulative response rate was 59% (partial response of 15% and complete response of 44%). The median time to respond was 30 days (Standard error [SE] 49) with a response rate of 44% at 4 weeks (95% Confidence interval: 29–62%). The multivariable Cox model analysis (variables include: age at diagnosis, gender, number of previous therapies and primary vs. secondary) revealed none of the variables included to be statistically significant. The cumulative rate of loss of response was 32% (6/19) with a median time to lose response of 54 months (SE, 0.03). In patients who lost response, the median time to lose response was 17 months (SE, 14). Of the 6 patients who lost response, 4 received a second course of rituximab and all 4 achieved a full response. No major side effects to rituximab were reported during the follow up. Conclusion: Rituximab is an effective and a well tolerated second line therapy for ITP. The response to rituximab can be maintained for a long duration with a high rate of response after retreatment. None of the pretreatment variables studied carried a significant predictive value for response. The study was limited by the small sample size and further larger prospective studies are recommended. Disclosures: Off Label Use: Rituximab was used in our study as a second line for the management of chronic immune thrombocytopenia.

Abstract 5304 Background: Non-transfused patients with thalassemia intermedia (TI) accumulate iron in their body due to increased gastrointestinal absorption of iron and release of iron from the macrophages. Earlier studies have revealed that serum ferritin does not reflect the severity of iron overload in non-transfused TI patients. The current study aims at evaluating the iron overload status in a group of young hypertransfused TI children. Materials and Methods: Eleven patients (mean age 13.18±4.094 years) with TI on regular follow-up at the Pediatric Thalassemia Day Care Centre, Sultan Qaboos University Hospital, Oman were included in the study after approval by the Medical Research and Ethics Committee. All patients had beta gene mutational analysis. They were diagnosed as intermedia because of their definitive TI mutation, late age at presentation (>5 years) and transfusion independence (mean baseline Hb 6.9 g/dl). Patients were treated conventionally with hypertransfusion, and chelation, as guided by their serum ferritin levels. Serum ferritin (2 monthly) was analyzed using the Beckman Coulter Access 2 Immunoassay System. Based on serum ferritin levels, patients were classified into 2 groups, group 1(six patients) and 2 (five patients) with serum ferritin levels below and above 1000 ng/ml respectively. All patients underwent cardiac T2* MRI assessment. Based on local reference values for T2*MRI, quantification of cardiac iron deposition was categorized as normal, mild, moderate and severe iron overload at values > 20 ms, 14–20 ms, 10–14 ms and < 10 ms respectively. Simultaneous liver iron T2* values were categorized into normal, mild, moderate and severe iron overload at values > 9.1 ms, 7.1–9.0 ms, 3.1– 7.0 ms and Results: Patients in group 1 and 2 had mean serum ferritin levels of 817.300±244.690 ng/ml and 1983.80±662.862 ng/ml respectively (p = 0.003). Despite this very high variation in serum ferritin values, T2* MRI showed comparable hepatic iron overload status in both the groups with mean hepatic T2* value of 2.51±0.46 ms and 3.4±1.63 ms in group 1 and group 2 respectively. The difference in hepatic T2* between the 2 groups is −0.88 (95% confidence interval −2.44 to 0.68) which is statistically insignificant (p =0.23, t-test). None of the studied patients had myocardial iron deposition (overall mean 36.86±7.8 ms). Other confounders like initial ages at presentation, pre-transfusion hemoglobin levels, durations of transfusion and chelation therapies were statistically insignificant for the 2 groups. No specific pattern of beta gene sequence was noted in either group. Conclusions: We conclude in our patients with TI on hypertransfusion, serum ferritin does not reflect their moderate to severe hepatic iron overload status. Inspite of steady serum ferritin trends, evaluation of iron overload by T2* MRI and optimal chelation is strongly recommended in hypertransfused TI patients. Disclosures: No relevant conflicts of interest to declare.

Abstract 5294 Background: Deferasirox is a relatively new once-daily oral iron chelator widely used for patients with thalassemia major. Efficacy of deferasirox has been evaluated in pediatric and adult patients with thalassemia and transfusion-dependent anemias. Experience with deferasirox in pediatric patients with thalassemia major is mainly in heavily iron loaded patients with a history of prior iron chelation. There are no current reports available on its use in chelation naïve very young patients with thalassemia major. Material and Methods: Ten chelation naive children (mean age 17.7 ± 2.7 months), on hypertransfusion regimen at the Pediatric Thalassemia Day Care Center, Sultan Qaboos University Hospital, Muscat, Oman, were initiated on deferasirox at a dose of 20 mg/kg/day at serum ferritin levels >500 ng/ml at a minimum age of 14 months. Patients were monitored and evaluated for possible side effects. Complete blood count, renal function test, liver function test and urine dipstick were done monthly with serum ferritin analysis once every 2 months. Guided by serum ferritin level and safety markers (transaminases, serum creatinine, and clinical adverse effects), the dose of deferasirox was gradually increased to 40 mg/kg/day with increments of 5 mg/kg/day every 2 months, in order to maintain a safe serum ferritin level with no major hepatic or renal side effects. Results: After a median treatment duration of 13 months (2–38 months) with deferasirox at a mean dose of 33.22 ± 5.99 mg/kg/day, mean serum ferritin level is 985.8 ± 373.002 ng/ml, as compared to baseline level of 807.8 ± 182.766 ng/ml. The increase in mean serum ferritin is 178 ng/ml (95% confidence interval −9.72 to 365.72) which is statistically insignificant (p = 0.06, two sided paired t-test). Nausea and vomiting, abdominal pain, and rash were observed in 1 patient each. Increase in transaminases was mild (3 times upper limit of normal) and non-progressive in 3 of the patients. Two patients had single serum creatinine level increases >33% above baseline and >upper limit of normal, and one had 2 non-consecutive increases requiring dose modification. The adverse effects were mild and did not require drug interruption. None of the patients had leucopenia, neutropenia or thrombocytopenia. Compliance with chelation was optimal. Conclusions: Deferasirox is relatively well tolerated in very young chelation naïve patients with thalassemia major. Dose increments of 5 mg/kg/day at intervals of 2 months allowed the optimization of the drug to 40 mg/kg/day within 1 year of initiation of chelation with no major adverse effects. Inspite of initial rises in serum ferritin at doses < 25 mg/kg/day, serum ferritin levels showed a steady trend towards the end of 12 months of therapy, requiring the continuation of the drug at doses > 30 mg/kg/day to achieve safe ferritin levels. Appropriate drug dosing guided by serum ferritin levels and safety markers improve the efficacy of deferasirox. Disclosures: Off Label Use: Deferasirox is a once-daily oral iron chelator used for patients with thalassemia major and other transfusion-dependent anemias. Experience with deferasirox in pediatric patients with thalassemia major is mainly in heavily iron loaded patients with a history of prior iron chelation. There are no current reports available on its use in chelation naïve patients with thalassemia major. We evaluated the efficacy of deferasirox in 10 very young chelation naïve children with thalassemia major.

Abstract 4105 Introduction: Conditioning chemotherapy prior to allogeneic bone marrow transplantation (BMT) can induce impairment in gonadal function. Patients with beta-thalassemia major generally undergo BMT at a young age and long-term data on its effects on gonadal function in this patient population are limited. Aims and objectives: To address the effect of BMT on gonadal function in long term survivors with beta-thalassemia major following successful BMT. Materials and methods: The hormonal profiles of gonadotrophins (LH and FSH), sex hormones (total and free testosterone in males, and 17 beta-estradiol in females) and inhibin B were assayed yearly after BMT. We analyzed data on patients who underwent BMT between January 1996 and June 2009 in whom the pubertal process should have started. Results: A total of 84 patients received BMT for thalassemia major; 51 (20 females and 31 males) have reached the age of puberty at the time of this analysis. Median age at transplant was 10 years (range: 3 – 17). With a median follow-up of 8 years (range: 2–15), the median age at last follow-up was 18 years (range: 13 – 26). All transplants were from matched sibling donors. Conditioning was myeloablative and consisted of: Busulfan, total dose of 600mg/m2 and Cyclophosphamide, total dose 200mg/kg (BuCy) before January 2005 and Busulfan, total dose 520mg/m2, Fludarabine, total dose 180mg/m2 and ATG, total dose 40mg/kg (BuFluATG) from January 2005 onwards. The impact of BMT appears to be different in the two sexes. 18 of 20 (80%) female patients had evidence of primary ovarian failure. Leydig cell failure was seen in only two male patients. However, injury to the germinal epithelium (as shown by low inhibin B levels which is predictive of oligo- or azoospermia) was seen in 22 of 31 (70%) male patients. A correlation was not found between the low inhibin B levels and age at BMT or type of conditioning regimen. Conclusion: Our data confirm that gonads in male and female thalassemic patients are affected by the cytotoxic effects of the preparative regimens of BMT, albeit at different levels. These findings emphasize the need for vigilant long term follow up of thalassemic patients post-BMT so that those requiring hormone replacement therapy can be identified and treated early. These findings are also important for pre- and post-BMT counseling. Disclosures: No relevant conflicts of interest to declare.

Abstract 2730 Background: Acute myeloid leukemia (AML) is a malignant myeloid disorder with heterogeneous outcomes. A number of factors have been shown to be prognostic; age, white blood cell (WBC), prior malignancy, performance status (Eastern Cooperative Oncology Group; ECOG) and cytogenetics. Methods: We planned to develop and validate a prognostic score for the 5-year (y) overall survival (OS) of adults with AML receiving intensive induction chemotherapy. We used Cox model to estimate the regression coefficients and Kaplan-Meier to estimate the 5-y OS. We used Cox-Snell, Schoenfeld and deviance residuals for model diagnostics and bootstrap validation to estimate the performance measures; Harrell's concordance and deviance residuals. Results: We retrospectively analyzed 779 patients treated between 1998–2008, using a prospectively collected database. The median age was 58 y. Most patients had intermediate risk cytogenetics (61%) and good performance status (ECOG 0–1: 79%). The median follow up for the surviving patients was 26.7 months (95% CI 18.8–32.9 months). The 5-y OS was 26% (22- 30%). All variables were statistically significant in the multivariable Cox regression model; age (y) (Hazard Ratio, HR 1.02; 95% CI 1.018–1.034), WBC (1*10^9/L) (HR 1.004; 1.002–1.006), prior malignancy (HR 1.58; 1.26–2.00), ECOG (ECOG 2 HR 1.41; 1.06–1.88, ECOG 3–4 HR 9.99; 4.72–21.18) and cytogenetics (intermediate risk HR 2.49; 1.41–4.39, poor risk HR 4.74; 2.65–8.50). The score divided patients into four risk groups; good (n=47), intermediate (n=129), poor (n=198) and extremely poor (n=87). The estimated 5-y OS was 0.70 (95% CI: 0.53–0.81), 0.37 (0.28–0.46), 0.15 (0.10–0.21) and 0.03 (0.01–0.10) respectively. The model showed good discrimination with large differences between survival curves and good Harrell concordance of 0.69. It showed good calibration using Cox-Snell and deviance residuals. In the intermediate risk cytogenetic group, the model showed good discrimination with over 45% difference in 5-y OS between the good and extremely poor groups. Conclusions: Our study confirmed the prognostic impact of the 5 variables reported in the literature. Using these factors, we developed a score to predict long term OS that showed good discrimination and calibration. The score added further discrimination in the intermediate risk cytogenetic group. Prospective external validation of the score is needed. Disclosures: No relevant conflicts of interest to declare.

Abstract 3184 Background: Osteonecrosis (ON) of the femoral and humeral heads is frequently seen in patients with sickle cell disease (SCD). Earlier studies reported a high prevalence of thrombophilia in patients with ON. Aims: To study the prevalence of thrombophilia in patients of SCD with ON. Methods: Case records of SCD patients with ON were retrospectively reviewed for protein S, protein C, and anti-thrombin deficiency, along with activated protein C resistance (APCR). Results: A total of sixty-three patients were identified, 35 of whom were males, with a median age of 21 years (range 15to 46). Median haemoglobin, total white cell count and platelet counts were 10 g/dL (range 7.7to 13.3), 7.5 ×109/L (range 3.4 to 16.7) and 302 ×109/L (range 72 to 1101) respectively. Twenty-eight patients were on hydroxyurea. Thrombophilia testing showed that 29% (95% confidence interval: 17–40), 47% (95% CI: 29–64) and 79% (95% CI: 65–93) of the patients had low levels of functional ( Summary/Conclusions: Patients with SCD and ON have a high prevalence of thrombophilia. These results indicate that a prospective study with more detailed thrombophilia work-up, along with confirmatory DNA analysis, as well as a study of the role of prophylactic anticoagulation in such patients is highly warranted. Disclosures: Pathare: Sultan Qaboos University: Employment, Research Funding. Alkindi:Sultan Qaboos University: Employment, Research Funding.

Abstract 2314 Poster Board II-291 Background: The impact of high dose therapy and autologous stem cell transplantation (ASCT) in the upfront management of adults with advanced follicular lymphoma (FL) on overall survival remains uncertain. A number of randomized clinical trials (RCTs) compared ASCT to conventional dose chemotherapy regimens. We performed a systematic review to address this question. Objective: To compare the overall survival (OS), event free survival (EFS), treatment related mortality (TRM), incidence of secondary myelodysplasia/acute myeloid leukemia (t-MDS/AML) and secondary solid tumors within the ASCT strategy and chemotherapy. Methods: We performed a search of MEDLINE, EMBASE, CENTRAL, American Society of Hematology (ASH), American Society of Clinical Oncology (ASCO), BIOSIS, PAPERSFIRST, PROCEEDINGS, clinical trials registries (National Cancer Institute, clinicaltrials.gov) and bibliographies of relevant studies for randomized controlled trials comparing myelo-ablative chemotherapy with ASCT to any chemotherapy in adults with untreated advanced (Ann Arbor stage III-IV) FL. Two reviewers recorded study characteristics, methodology and outcomes. Disagreement was resolved by discussion. Results: Seven trials were identified and included in the systematic review but only four with available data reporting 941 patients were included in the meta-analysis. Three trials excluded: one was never reported; the second was stopped early due to the increased toxicities in the transplant arm; and the third showed no significant difference in EFS or OS at an interim analysis with insufficient data for the meta-analysis. None of these studies has been published. In one of the 7 trials patients in both arms received rituximab during the induction treatment. High dose therapy and ASCT did not result in improved OS compared to standard therapy, Hazard Ratio (HR) 1.15 (0.85, 1.55). The HR for EFS was 0.61 (0.34, 1.11) with substantial heterogeneity, I2 =91%, Chi2 p value Conclusions: High dose therapy and ASCT as part of initial does not improve overall survival despite a trend towards better disease control, likely because of the effectiveness of second and subsequent lines of treatment for FL. T-MDS/AML occurs more commonly following ASCT and represents a significant risk to patients. With one exception, these studies were conducted before the introduction of monoclonal B cell antibodies. Future trials of ASCT in the context of current chemo-immunotherapy approaches to FL would further inform this issue. Disclosures: No relevant conflicts of interest to declare.

Abstract 1202 Poster Board I-224 Introduction: The eligibility of patients to undergo allogeneic hematopoietic cell transplantation (AHCT) is limited by age, co-morbid conditions and performance status. Utilizing reduced and minimal intensity conditioning regimens, older and less fit patients could benefit from this modality with the graft versus leukemia effect. Methods: We performed a retrospective analysis of adults aged 40-60 years with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing AHCT at our center from January 2002 to June 2008. The objective of the study is to compare the overall (OS), relapse free (RFS), acute GvHD free and chronic GvHD free survival between the different conditioning regimens. The regimens are classified according to the definition of CIBMTR as conventional intensity (CIC) or reduced intensity (RIC). High risk disease is defined as patients meeting one of the following criteria: AML with poor risk cytogenetics, secondary AML with preceding hematologic disorder, AML in second complete remission or AML/MDS with preceding malignancy. Results: There are 106 patients eligible for the study (CIC 67, RIC 39); 56 patients with de novo AML, 22 with MDS and 28 with secondary AML. High risk disease comprised 64% of our study population. The baseline characteristics between the two groups including performance status (Karnofsky Performance Score; CIC 81%, RIC 83%, p=0.08) are not different except for age (mean in years; CIC 50.2, RIC 52.9, p=0.03), graft versus host disease (GvHD) prophylaxis (cyclosporine/alemtuzumab; CIC 16%, RIC 57%, p Conclusion: Despite inferior baseline characteristics in the patients receiving RIC, the outcomes were similar. Disease biology rather than intensity of the conditioning therapy is the determinant of overall survival and relapse risk after AHCT in patients aged 40-60 years with AML/MDS. Prospective randomized studies are needed to determine the superiority of RIC in patients who are deemed suitable to undergo CIC. Disclosures: No relevant conflicts of interest to declare.

T cell acute lymphoblastic leukemia (T-ALL) accounts for 14–22% of adult ALL. No prospective comparisons between different chemotherapy protocols have been done. Since 2000 a modified DFCI protocol (Silverman et al, Blood2001;97:121–1218) has been used as standard treatment for all newly diagnosed patients with T-ALL at Princess Margaret Hospital (PMH). This protocol includes a remission induction phase, a CNS prophylaxis phase with intrathecal chemotherapy and 12 Gy cranial irradiation, a 30-week intensification phase including weekly asparaginase, and a 72-week maintenance phase. We compared outcomes using this regimen to previous results for all newly diagnosed T-ALL from 1990 – 2000 at PMH using the standard institutional protocol in use at the time. Between 1990–2000, 44 patients (Group 1) were treated with a variety of protocols, including 9203ALL PMH protocol (11 patients), L10 (2 pts), Protocol C (7 pts), HyperCVAD (15 pts) and ECOG E2993 (9 pts). From 2000–2007, 33 T-ALL patients were treated with modified DFCI protocol (Group 2). The median age for all patients was 31 years (range 14–69 years). There was no significant difference between the two groups with respect to age at diagnosis, presenting WBC (median or percent > 100 ×109/L), CSF positivity, or cytogenetics. More patients from Group 1 underwent allogeneic stem cell transplantation (BMT) in CR-1 (54%) as compared to those in Group 2 (54% vs. 14%, P = 0.001), primarily due to a change in BMT policy in 2002. The median follow up was 23 months (range 1–161 months) for the entire group and 53 months (range 14–161 months) for the surviving patients. Sixty-nine patients (90%) achieved complete remission, and 37 patients have relapsed. The CR rates were not significantly different between the two groups. The 3-year failure-free survival (FFS) was significantly higher in Group 2 (DFCI protocol) as compared with Group 1 (other protocols) (89% vs. 27%, P = 0.0001). Multivariate analysis using Cox proportional hazard model showed only the treatment regimen received (DFCI vs. others) to have a statistically significant impact on FFS (P = 0.0001). The 3-year overall survival (OS) was significantly higher in the DFCI group compared to the group receiving the other protocols (81% vs. 45%, P = 0.0006). On multivariate analysis, only the treatment regimen received (P=0.001) and the CSF status (P=0.014) had a significant impact on OS; BMT did not have a significant impact on OS. When patients were censored at the time of transplant, the FFS and OS analyses still showed statistically significant benefit for patients treated on DFCI protocol (P = 0.0001 and 0.03, respectively). In summary, treatment outcomes have markedly improved from 2000 onward as compared to the previous decade. Although improvements in supportive care and reduced use of allogeneic BMT may have been factors, it is likely that the institution of the DFCI pediatric protocol was the primary factor in the improved outcome. These results support the use of such pediatric asparaginase-intensive pediatric protocols for adult T-ALL.

We retrospectively reviewed our experience of 63 adult T-ALL patients to identify clinical and pathologic prognostic factors and build a risk-stratification model for induction chemotherapy. At presentation, the patients’ median age was 30, 49 were male and 14 female, 69% had lymphadenopathy, 38% a mediastinal mass, 24% CNS involvement and 21% splenomegaly. The median initial WBC was 17.9 x 109/L (range 0.10–510.0). Blasts expressed CD34 in 42% of cases, CD10 in 33% and at least one myeloid-associated antigen (CD13 or CD33) in 27%. Karyotypes were abnormal in 34% of cases. Fifty-three of 61 patients (87%) who underwent induction chemotherapy achieved complete remission (CR) on protocols including vinca alkaloids, anthracyclines and corticosteroids. On univariate analysis; age, gender, initial WBC, CD10, CD34 and abnormal karyotype did not predict CR but patients expressing at least one myeloid-associated antigen had a CR of 71% compared to 93% (P=0.03) for patients not expressing myeloid antigens. The median follow-up was 19.2 months (95% CI: 0.1–172.8). Twenty-three patients relapsed with a median relapse-free survival (RFS) of 41.6 months (95%CI: 21.6–55.9). The RFS was longer for patients with an initial WBC of 3–50 x 109 and for cases expressing CD10 but neither was statistically significant (P=0.19, P=0.14). On follow-up, 34 patients died with a median overall survival (OS) of 31.3 months (95%CI: 16.8–56.8). Patients with CD10 expression had a longer median OS at 44.7 months (versus 19.2 months for CD10 negative patients) but again, the difference was not statistically significant (P=0.11). Age, gender, CD34, myeloid-associated antigen expression and karyotype did not influence RFS or OS. Our study indicates that expression of myeloid-associated antigens is an adverse prognostic factor for complete remission of adult T-ALL and should be considered for induction chemotherapy risk-stratification.