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We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes., Turkish Society of Pediatric Hematology, We would like to thank Vedat Uygun for contributing to the statistics of the study. This study was supported by the Turkish Society of Pediatric Hematology.

Objectives BK virus-associated hemorrhagic cystitis is a common complication of allogeneic hematopoietic stem cell transplant. It is known to be associated with cyclophosphamide therapy and the intensity of the conditioning regimen as well as infection with the BK virus. Data are limited for BK virus-associated hemorrhagic cystitis in pediatric recipients of allogeneic hematopoietic stem cell transplant. Therefore, we aimed to identify the risk factors and etiology of BK virus-associated hemorrhagic cystitis and determine the factors that may improve the treatment efficacy. Materials and methods Data from recipients of allogeneic hematopoietic stem cell transplant were retrospectively analyzed. These data included information about age, sex, underlying disease, the details of ablative conditioning, graft-versus-host disease prophylaxis, donor type, stem cell source, history of acute graft-versus-host disease, and cytomegalovirus reactivation. Results A total of 50 patients developed BK virusassociated hemorrhagic cystitis among 334 patients. Symptoms associated with BK virus-associated hemorrhagic cystitis manifested an average of 45.3 days after transplant. Most of the patients had grade 2 and grade 3 hemorrhagic cystitis. Risk factor analysis revealed that haploidentical donor type, treatment with busulfan and cyclophosphamide as part of conditioning regimen, and history of total body irradiation increased the risk of BK virus-associated hemorrhagic cystitis in the pediatric recipient population. Conclusions We found that, despite current conditioning regimens, BK virus-associated infection still leads to a considerable incidence rate of hemorrhagic cystitis in pediatric recipients of allogeneic hematopoietic stem cell transplant. Patients with a haploidentical donor and a history of busulfan and cyclophosphamide treatment or total body irradiation had a higher risk of BK virus-associated hemorrhagic cystitis. Thus, we suggest that patients with these factors should be followed closely after allogeneic hematopoietic stem cell transplant.

This study aimed to observe the preventive effect of prophylactic treatment on joint health in people with hemophilia (PwH) and to investigate the importance of integration of ultrasonographic examination into clinical and radiological evaluation of the joints.This national, multicenter, prospective, observational study included male patients aged ≥6 years with the diagnosis of moderate or severe hemophilia A or B from 8 centers across Turkey between January 2017 and March 2019. Patients were followed for 1 year with 5 visits (baseline and 3Seventy-three PwH, of whom 62 had hemophilia A and 11 had hemophilia B, were included and 24.7% had target joints at baseline. The HJHS and HEAD-US scores were significantly increased at the 12The HEAD-US and HJHS scoring systems are valuable tools during follow-up examinations of PwH and they complement each other. We suggest that POC ultrasonographic evaluation and the HEAD-US scoring system may be integrated into differential diagnosis of bleeding and long-term monitoring for joint health as a routine procedure.Bu çalışmada hemofili hastalarında profilaksinin eklem sağlığı üzerindeki koruyucu etkisini gözlemlemek ve eklemlerin klinik ve ultrasonografik olarak değerlendirilmesinin öneminin araştırılması amaçlandı.Ulusal, çok merkezli, prospektif ve gözlemsel olan araştırma Ocak 2017 - Mart 2019 arasında 8 ayrı merkezde takip edilen erkek ve 6 yaşından büyük orta seviyede veya ağır hemofili-A ve hemofili-B hastalarını kapsıyordu. Hastalar 1 yıllık takip sırasında toplam 5 ayrı vizitte (başlangıç, 3. ay, 6. ay, 9. ay ve 12. ay) değerlendirildi. Hemofili Eklem Sağlığı Skoru (HJHS) eklemlerin fiziksel bakısında kullanılırken Petterson skorlama sistemi radyolojik bakı sırasında değerlendirildi. Ayrıca, hasta başı ultrasonografisiyle bilateral eklem incelemeleri yapılarak HEAD-US skorlama yöntemiyle eklem skorları belirlendi.Çalışmada 62’si hemofili A ve 11’I hemofili B olan 73 hastanın %24,7’sinde hedef eklem varlığı mevcuttu. HJHS ve HEAD-US skorlarının tüm hastalarda takibin 12. ayında anlamlı olarak arttığı gözlendi. Hemofili A hastalarında daha yüksek skorlar saptandı. Skor artımı alt gruplarda değerlendirildiğinde çocukluk yaş grubunda artışın anlamlı olmadığı gözlendi. Başlangıçta ve 12. ayda yapılan üçlü bakıda HJHS, HEAD-US ve Petterson skorlarının anlamlı olarak korele olduğu saptandı.HJHS eklem skoru ile HEAD-US radyolojik skorlamasının hemofili hastalarının eklem sağlığının takibinde çok değerli olup birbirlerini destekledikleri yakından gözlendi. Hasta başı US skorlama sistemlerinin günümüzde hemofilide eklem sağlığının rutin takip ve izlemi sürecinde hem kanama ayırıcı tanısı hem de uzun dönemli takip açısından oldukça değerli bir yeri olacağını düşünüyoruz.

Objective The study aimed to compare the effects of three different methods of umbilical cord management on hematological parameters in term and late-preterm infants. Study Design A randomized controlled trial comparing intact-umbilical cord milking (I-UCM) with cut-umbilical cord milking (C-UCM) and immediate cord clamping (ICC) in neonates born >35 weeks' gestation. Results A total of 587 infants were evaluated. Of these, 197 were assigned to I-UCM, 190 to C-UCM, and 200 to ICC. Mean hemoglobin and hematocrit levels at 48 hours of age were higher in I-UCM group compared with the ICC group (p = 0.002 and p = 0.010, respectively). Conclusion These findings suggest that I-UCM is more beneficial choice. Further trials are needed to assess the various long- and short-term effects of different cord milking methods. Key Points

Objective: Hemophilia A is the second most common bleeding disorder causing patients to have lifelong follow-up and treatment. Despite being a rare disease, hemophilia A has a high economic burden on individuals and the public. The purpose of this study was to estimate the total disease cost of hemophilia A in Turkey. Materials and Methods: Data used in this analysis were collected through literature review, including studies conducted in Turkey in December 2018. A disease burden analysis was performed by modeling hemophilia A-related costs among patients, their relatives, and the social security system. Two expert panels were held to evaluate real-world data sources and to provide further information. All direct medical and non-medical costs were calculated annually from the Social Security Institution of the Republic of Turkey perspective, while indirect costs were estimated from the patient and community perspective. Results: For the calendar year of 2018, the number of hemophilia A patients in Turkey were estimated to be 5,055, with an average weight of 64.7 kg. The average annual direct medical, direct non-medical, and indirect costs of hemophilia A were calculated as euro93,268 ($109,286; (sic)502,717), euro2,533 ($2,968; (sic)13,655), and euro7,957 ($9,323; (sic)42,888) per patient, respectively, with a total annual cost of euro103,759 ($121,578; (sic)559,259). For the management of patients with inhibitors (4.9%), the average annual total cost was calculated to be euro325,439 ($381,330; (sic)1,754,117) per patient. The total annual disease burden of hemophilia A in 2018 was estimated to be about euro524 million ($614 million; (sic)2.82 billion), which corresponded to 1.6% of the total health expenditure in Turkey. Conclusion: The most important reason hemophilia A has a significant economic burden in Turkey is that replacement therapy is expensive. The major cost contributor was identified as factor replacement therapy. With inhibitor development, the average annual cost increased more than 3-fold., Roche Mustahzarlari Sanayi A.S., Roche Mustahzarlari Sanayi A.S. provided a study grant for medical writing support, which was provided by Pleksus Clinical Research, Istanbul, Turkey. Roche or Pleksus has not influenced the content of this study.

ÖZET Amaç: Hastanemizde gelişen hastane enfeksiyonuna (HE) neden olan etkenlerin dağılımı ve antibiyotik duyarlılıklarının belir lenmesi. Hastalar ve yöntem: Yaklaşık 116 yatak kapasiteli hastanemizde, Ocak 2017 – Aralık 2017 tarihleri arasındaki hastane enfeksiyon ları surveyans yöntemi ile retrospektif olarak değerlendirildi. Bulgular: Ocak 2017-Aralık 2017 tarihleri arasında Acıbadem Adana Hastanesinde 9931 hasta yatışı yapıldı. Hastaların 92’sinde hastane enfeksiyonu geliştiği saptandı. Tüm hastane genelinde enfeksiyon hızı %1,32 idi. HE dağılımı; 30 hastada bakteriyemi (%29,4), 22 hastada cerrahi alan enfeksiyonu (%21,5), 20 hastada üriner sistem enfeksiyonu (%19,6) ve 15 hastada pnomoni (%14,7) olarak saptandı. Çocukluk yaş grubunda bakteriyemi ve pnömoni, yetişkin yaş grubunda ise üriner sistem ve cerrahi alan enfeksiyonu en sık sapta nan HE idi. HE gelişen hastaların %97,7’de bir ya da daha fazla etken izole edilirken, %2,3’de herhangi bir etken izole edilemedi. Hastane genelinde en sık izole edilen mikroorganizmalar sırasıyla; Klebsiella spp. (%29,5), E.coli (%22,7), maya mantarları %20 ,5 ve S.aureus (%9) idi. HE en sık olarak onkoloji servisinde (%57,8), genel yoğun bakım ünitesinde (%24,5) ve pediatrik kemik iliği ünitesinde (%17,6) görüldü. Sonuçlar: HE yataklı tedavi kurumlarının hizmet kalitesinin önemli göstergelerinden biri olup artık tüm dünyada önemli bir sağ lık sorunu olarak görülmektedir. HE önlemek için düzenli olarak surveyans çalışmaları yapılarak elde edilen sonuçlar düzenli bir şekilde takip edilmeli, ayrıca gereksiz invaziv işlemlerden kaçınılmalıdır. Tüm hastaneler ve hastane içinde birimlerin; hastane enfeksiyonuna neden olan mikroorganizmaları ve bunların direnç oranlarını surveyans çalışmaları ile belirlemeleri, tedavi karar larını buna göre vermeleri gerekir.

Haemophilia is an X-linked lifelong congenital bleeding disorder that is caused by insufficient levels of factor VIII (FVIII; haemophilia A) or factor IX (FIX; haemophilia B) and characterized by spontaneous and trauma-related bleeding episodes. The cornerstone of the treatment, factor replacement, constitutes several difficulties, including frequent injections due to the short half-life of recombinant factors, intravenous administration and the risk of inhibitor development. While extended half-life factors and subcutaneous novel molecules enhanced the quality of life, initial successes with gene therapy offer a significant hope for cure. Although adeno-associated viral (AAV)-based gene therapy is one of the most emerging approaches for treatment of haemophilia, there are still challenges in vector immunogenicity, potency and efficacy, genotoxicity and persistence. As the approval for the first gene therapy product is coming closer, eligibility criteria for patient selection, multidisciplinary approach for optimal delivery and follow-up and development of new pricing policies and reimbursement models should be concerned. Therefore, this review addresses the unmet needs of current haemophilia treatment and explains the rationale and principles of gene therapy. Limitations and challenges are discussed from a global and national perspective and recommendations are provided to adopt the gene therapies faster and more sufficient for the haemophilia patients in developing countries like Turkey.

Background Management of severe hemophilia A includes on-demand treatment or prophylaxis with replacement factor VIII (FVIII) concentrate. FVIII inhibitors can develop following exposure to exogenous FVIII in approximately 30% of previously untreated patients (PUPs), typically in the first 50 exposure days (EDs), with serious complications. This is the first study evaluating the safety, immunogenicity, and hemostatic efficacy of rurioctocog alfa pegol (Adynovate ®; Baxalta US Inc., a Takeda company, Lexington, MA, USA), an extended half-life (EHL) recombinant FVIII, in PUPs with severe hemophilia A. Methods This prospective, open-label, multi-center, phase 3 study (NCT02615691) was conducted in patients ˂6 years of age with severe hemophilia A (FVIII Results As of the data cut-off, 59 (73.8%) of 80 enrolled patients had received ≥1 dose of rurioctocog alfa pegol; 18 patients (screen failures) did not meet the eligibility criteria and 4 discontinued prior to treatment. 54 patients received prophylaxis and 35 received on-demand treatment at any time during the study period. The mean (SD) patient age at baseline was 11.8 (8.2) months. The number of patients with 0 EDs prior to screening was 36 (61.0%), with 9 (15.3%) patients having 1 ED and 14 (23.7%) having 2 EDs. Overall, 32 patients had a family history of hemophilia A. A large deletion, intron 1 or intron 22 inversion, or substitution nonsense hemophilia gene mutation was present in 29 (49.2%) patients and 21 (35.6%) had either a small deletion, small duplication, or substitution missense gene mutation. Of the 52 patients who qualified for this interim analysis, 10 developed an inhibitory antibody to rurioctocog alfa pegol during the study; the incidence of inhibitor development was 0.192 (95% CI, 0.096-0.325) (10/52). Rurioctocog alfa pegol exposure data and ABRs for patients receiving prophylaxis or on-demand treatment are presented in Table 1. At bleed resolution, hemostatic efficacy was rated by patients as "excellent" for 88/269 bleeds (32.7%) and "good" for 73/269 bleeds (27.1%). Overall, 52 (88.1%) patients receiving rurioctocog alfa pegol experienced a total of 283 AEs, and 13 patients experienced 14 rurioctocog alfa pegol-related AEs (including 10 SAEs). SAEs occurred in 24 patients, 10 of whom experienced 10 treatment-related SAEs of FVIII inhibitor development. Discussion This is the first prospective study of the EHL recombinant FVIII rurioctocog alfa pegol for the treatment of PUPs with severe hemophilia A. These preliminary results demonstrate a relatively low inhibitor rate compared with other EHL recombinant FVIII products and a safety and efficacy profile consistent with that previously observed for rurioctocog alfa pegol in the treatment of bleeding episodes in patients with hemophilia A. Figure 1 Figure 1. Disclosures Sidonio: Guardian Therapeutics: Consultancy; Pfizer: Consultancy; Bayer: Consultancy; Octapharma: Consultancy, Research Funding; Novo Nordisk: Consultancy; Biomarin: Consultancy; Genentech: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Catalyst: Consultancy. Peyvandi: Takeda: Honoraria; Spark: Honoraria; Sobi: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Roche: Honoraria; Bioverativ: Honoraria; Grifols: Honoraria. Stasyshyn: Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding; Shire: Consultancy; Grifols: Consultancy, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau. Antmen: Takeda: Consultancy; Pfizer: Consultancy; Roche: Consultancy; Novo Nordisk: Consultancy. Yeoh: Takeda: Honoraria; Pfizer: Honoraria; Roche: Honoraria; Grifols: Honoraria. Maggiore: IQVIA: Current Employment. Engl: Baxalta Innovations GmbH, a Takeda company: Current Employment; Takeda: Current equity holder in publicly-traded company. Allen: Takeda Development Center Americas, Inc.: Current Employment; Takeda: Current equity holder in publicly-traded company. Tangada: Takeda: Current equity holder in publicly-traded company; Takeda Development Center Americas, Inc: Current Employment.

FK506 (tacrolimus) is an immunosuppressive drug and more potent than cyclosporine. FK506 is widely used for immunosuppression in the prevention and treatment of graft-versus-host disease after allogeneic bone marrow transplantation and solid organ transplantation. Neurotoxicity is a recognized complication of FK506 therapy, but ptosis and weakness of eye abduction unilaterally has not been reported in association with FK506 administration to date. We discuss a 13-year-old male patient who developed ptosis and weakness of eye abduction unilaterally 90 days after transplantation with bone marrow from an unrelated donor, for acute lymphoblastic leukemia in this case report. FK506 therapy was administered for graft-versus-host disease prophylaxis and CMV infection was treated with ganciclovir. The physical examination findings completely resolved 72 to 96 hours after concomitant FK506 and ganciclovir treatment were terminated.

ispartof: HAEMATOLOGICA vol:104 issue:8 pages:E335-E339 ispartof: location:Italy status: published

PubMedID: 30300449 Objectives: To evaluate the long-term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion-dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey. Methods: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (?100 mL/kg of pRBC or a serum ferritin [SF] level >1000 µg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice. Results: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 µg/L (P

WOS: 000490575700006 Aim: Visceral leishmaniasis (VL) is a systemic infection that spreads hematogenously and affects the reticuloendothelial system by the infection of macrophages. VL occurs commonly in children, and only rarely in adults. VL should be considered in patients with prolonged high fever, hepatosplenomegaly, pancytopenia, weight loss, pallor and hypergammaglobulinemia. Materials and Methods: In this study, a total of 18 pediatric patients -9 (50%) males and 9 (50%) females- treated for VL at our clinic from January 2004 to July 2014 were analyzed retrospectively. Average time from symptom onset to hospital admission was 64 +/- 21 days (range: 30-100 days). The mean age of patients was 88 +/- 40 months (range: 36-182 months). Results: The most common symptom at presentation was fever (88.9%). Other common symptoms were fatigue, chills, weight loss and anorexia. Physical examination revealed splenomegaly and hepatomegaly in all patients. Anemia (92.4%), leukopenia (78.7%) and thrombocytopenia (76.2%) were the most prominent laboratory abnormalities and 82.2% of the patients were pancytopenic on admission. Bone marrow smear was positive for leishmania in 100% of the patients. All patients received treatment with liposomal amphotericin B. Conclusion: In certain regions, increased humidity rates associated with construction of dams and irrigation canals may lead to changes in the ecological balance and thus cause an increase in the population of disease-spreading vectors. Additionally, recent migration from the middle-eastern region to western parts of the world due to regional civil wars may have contributed to the observed increase in the incidence of various diseases such as VL.

10th Eurasian Hematology Oncology Congress -- OCT 08-11, 2019 -- Istanbul, TURKEY WOS: 000489290100006 …

BACKGROUND AND OBJECTIVES We aimed to evaluate joint health in children with hemophilia (CwH) and to investigate the effects of hemarthrosis on the musculoskeletal system. METHOD Forty-one CwH aged between 6-18 years participated in the study. Joint health status was evaluated according to Hemophilia Joint Health Score (HJHS). Pain intensity level was assessed in resting and in activity using Visual Analog Scale. Range of motion was measured with goniometer and muscle strength was assessed with digital dynamometer. Arthropathic joints were examined in three groups named knee, elbow and ankle. RESULTS Physical examination revealed arthropathy findings to be found in 29 knee, 19 elbow and 18 ankle joints. The median of flexion angle of the affected side were 120°, 122° and 12° for the knee, elbow and ankle and extension losses of these joints were 5°, 7° and 0, respectively. In CwH having knee and elbow arthropathy, index joint HJHS was found to be significantly higher than those with ankle arthropathy (p < 0.01). The flexor and extensor muscle strength significantly decreased in 11 CwH with unilateral elbow arthropathy compared to the non-arthropatic side (p < 0.05). In 15 CwH with unilateral ankle arthropathy decreased in the extensor muscle strength (plantarflexors) (p < 0.05). Extension loss showed a good correlation with index HJHS of elbow, knee and ankle joints, respectively. (rs= 0.599, 0.576, 0.606, p < 0.01). We observed that the muscle strength of elbow flexors/extensors and ankle extensors were significantly decreased compared to the non-arthropathic side. However this situation was not detected in knee joint despite having highest index HJHS. CONCLUSION Our findings indicate that hemarthrosis may cause more muscle strength loss in the upper extremity than the lower extremity. Furthermore, extension loss was found to be an important parameter in physical examination of hemophilic arthropathy. Musculoskeletal system should be evaluated comprehensively at regular intervals and when necessary rehabilitative treatment should be planned.

PubMedID: 30690828 Introduction: Among children with haemophilia and their caregivers; problems arising from the teeth and the surrounding tissues have an important role in the treatment of this disease and it affects the quality of life of children and their parents. Aim: Aim of this study is to evaluate the oral health-related quality of life of children with haemophilia from the perspective of their parents. Methods: Paediatric oral health-related quality of life (POQL) instrument was used in this cross-sectional study for quality of life measurement. The research data collected by the questionnaire form were coded for scale items and personal information questions and transferred to SPSS, a multivariate statistical analysis program for social sciences. SPSS 23.0 (IBM Corp, Armonk, NY) package program was used for statistical analysis of the data. Results: Primary dentition dmft scores of patients with haemophilia are higher than the control group; mean value of haemophilic group is 3.5 vs control group are 2.6, respectively (P = 0.034). In spite of higher dmft scores, the haemophilia and control groups have shown no significant difference in oral health-related quality of life scores; median scores were 63.9 in haemophilic group and 85.3 in control group (P = 0.336), respectively. Conclusion: In spite of lower oral health measures, children with haemophilia and their parents reported no difference in oral health-related quality of life from their healthy counterparts. © 2019 John Wiley & Sons Ltd

Thalassemias are a heterogeneous group of autosomal recessive diseases characterized by hypochromic microcytic anemia and occur as a result of defective synthesis of one or more hemoglobin chains. In patients, life-threatening clinical manifestations may occur because of severe iron overload due to frequent blood transfusions. Ocular changes in patients with thalassemia are to be encountered depending on the disease itself or chelator used in the treatment, but not very often. These changes are usually cataracts, optic neuropathy, retinal pigment epithelium (RPE) degeneration, RPE mottling, retinal venous tortuosity, vitreoretinal hemorrhages and obliteration of the iris pattern. Desferrioxamine that is used as the first iron-binding chelating has well-known complications such as optic neuropathy and retinal toxicity. However, Deferiprone that used more common recently has replaced the Desferrioxamine but, there is very little information in the literature about the ocular toxicity of deferiprone. In this case report, we have reported a patient with deferiprone-induced cataract formation in order to draw attention to a little-known complication of the drug., Talasemiler; otozomal resesif kalıtım gösteren, hemoglobin zincirlerinden birinin veya bir kaçının hasarlı sentezi sonucu ortaya çıkan hipokrom mikroster anemi ile karakterize heterojen bir grup hastalıktır. Hastaların sık transfüzyona maruz kalması sonucunda aşırı demir birikimine bağlı yaşamı tehdit eden önemli klinik bulgular ortaya çıkar. Talasemili hastalarda hastalığın kendisine ya da kullanılan şelatör tedavisine bağlı olarak oküler değişikliklere çok sık olmasa da rastlanmaktadır. Bu değişiklikler genellikle katarakt, optik nöropati, retinal pigment epitelinde (RPE) dejenerasyon, RPE mottling, retinal venous tortuosity, vitreoretinal hemorrhages and obliteration of iris patern şeklindedir. İlk defa demir bağlayıcı şelatör olarak kullanılmaya başlanan deferoxamin optik nöropati ve retinal toksisite gibi iyi bilinen komplikasyonlara sahiptir. Ancak deferoxaminin yerini alan ve yakın dönemde sık kullanılan deferipronun oküler toksisitesi ile ilgili literatürde daha önce bildirilmiş az sayıda bilgi vardır. Bu olgu deferipron kullanımına bağlı gelişen katarakt oluşumuna dikkat çekmek amacıyla bildirilmiştir.

Talasemiler; otozomal resesif kalıtım gösteren, hemoglobin zincirlerinden birinin veya bir kaçının hasarlı sentezi sonucu ortaya çıkan hipokrom mikroster anemi ile karakterize heterojen bir grup hastalıktır. Hastaların sık transfüzyona maruz kalması sonucunda aşırı demir birikimine bağlı yaşamı tehdit eden önemli klinik bulgular ortaya çıkar. Talasemili hastalarda hastalığın kendisine ya da kullanılan şelatör tedavisine bağlı olarak oküler değişikliklere çok sık olmasa da rastlanmaktadır. Bu değişiklikler genellikle katarakt, optik nöropati, retinal pigment epitelinde (RPE) dejenerasyon, RPE mottling, retinal venous tortuosity, vitreoretinal hemorrhages and obliteration of iris patern şeklindedir. İlk defa demir bağlayıcı şelatör olarak kullanılmaya başlanan deferoxamin optik nöropati ve retinal toksisite gibi iyi bilinen komplikasyonlara sahiptir. Ancak deferoxaminin yerini alan ve yakın dönemde sık kullanılan deferipronun oküler toksisitesi ile ilgili literatürde daha önce bildirilmiş az sayıda bilgi vardır. Bu olgu deferipron kullanımına bağlı gelişen katarakt oluşumuna dikkat çekmek amacıyla bildirilmiştir. Thalassemias are a heterogeneous group of autosomal recessive diseases characterized by hypochromic microcytic anemia and occur as a result of defective synthesis of one or more hemoglobin chains. In patients, life-threatening clinical manifestations may occur because of severe iron overload due to frequent blood transfusions. Ocular changes in patients with thalassemia are to be encountered depending on the disease itself or chelator used in the treatment, but not very often. These changes are usually cataracts, optic neuropathy, retinal pigment epithelium (RPE) degeneration, RPE mottling, retinal venous tortuosity, vitreoretinal hemorrhages and obliteration of the iris pattern. Desferrioxamine that is used as the first iron-binding chelating has well-known complications such as optic neuropathy and retinal toxicity. However, Deferiprone that used more common recently has replaced the Desferrioxamine but, there is very little information in the literature about the ocular toxicity of deferiprone. In this case report, we have reported a patient with deferiprone-induced cataract formation in order to draw attention to a little-known complication of the drug.

PubMedID: 23731246 Patients with haemophilia A and inhibitors are at high risk for severe bleeding, progression of joint disease and deterioration of health-related quality of life (HRQoL). To determine the impact of prophylaxis with an activated prothrombin complex concentrate (aPCC) on HRQoL, HRQoL was assessed using the Short-Form (SF)-36 Health Survey and the EQ-5D questionnaire in subjects ?14 years participating in a prospective, randomized, crossover study comparing 6 months of aPCC prophylaxis with 6 months of on-demand therapy. Eighteen of 19 patients completed the survey or questionnaire before and after the on-demand therapy and prophylaxis periods. A general trend towards improved HRQoL after prophylaxis was observed for the 18 evaluable patients in all SF-36 dimensions except for vitality/energy and physical functioning. After prophylaxis, 'good responders,' defined as patients experiencing ?50% reduction in bleeding, exhibited statistically and clinically significant differences in the physical component score (P = 0.021), role - physical (P = 0.042), bodily pain (P = 0.015), and social functioning (P = 0.036). Similarly, the EQ-5D health profile showed a trend towards improvement after prophylaxis in all evaluable patients. Among the good responders, improvements did not differ from those observed after on-demand treatment. EQ visual analogue scale values were slightly improved following prophylaxis for all evaluable patients and the EQ-5D utility index improved in the good responders only. During prophylaxis, patients missed significantly fewer days from school or work because of bleeding than during on-demand treatment (P = 0.01). In conclusion, by significantly reducing bleeding frequency in good responders, aPCC prophylaxis improved HRQoL compared with on-demand treatment. © 2013 John Wiley & Sons Ltd.

WOS: 000376443500008, PubMed ID: 27223147, BACKGROUND The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. METHODS We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age = 5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). CONCLUSIONS Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.), Angelo Bianchi Bonomi Foundation, Funded by the Angelo Bianchi Bonomi Foundation and others

WOS: 000453162300036 Following joint hemorrhages, intramuscular hemorrhages are the second most prevalent bleeding pattern in hemophiliac patients. Hematomas of the iliopsoas muscle are a well-known complication of hemophilia; however, obturator muscle hematomas are rare. We herein report a case of spontaneous bleeding of the bilateral external obturator muscles, which occured three times within a period of 9 months in a hemophilia patient with factor VIII inhibitors. To the best of our knowledge, this is the first published case of an obturator externus muscle hematoma in hemophilia. In addition to hip hemarthrosis, iliopsoas hematomas and acute appendicitis, obturator muscle hematoma should be considered as one of the diagnostic alternatives for pelvic pain in hemophilia. patients. Magnetic resonance imaging enables rapid diagnosis of obturator muscle hematoma.

PubMedID: 22509726 This study aimed to determine the effect of haemolysis on plasma oxidation and nitration in sickle cell disease (SCD) patients. Blood was collected from haemoglobin (Hb)A volunteers and homozygous HbSS patients who had not received blood transfusions in the last 3 months. Haemolysis was characterised by low levels of haemoglobin and haptoglobin and high levels of reticulocyte, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), plasma cell-free haemoglobin, bilirubin, total lactate dehydrogenase (LDH) and dominance of LDH-1 isoenzyme. Plasma 8-isoprostane, protein carbonyl and nitrotyrosine levels were measured to evaluate oxidised lipids, oxidised and nitrated proteins, respectively. Plasma nitritenitrate levels were also determined to assess nitric oxide (NO) production in both SCD patients and controls. Markers of haemolysis were significantly evident in SCD patients compared to controls. Plasma 8-isoprostane, protein carbonyl and nitrotyrosine levels were markedly elevated in SCD patients compared to controls. Linear regression analysis revealed a significant inverse correlation between haemoglobin and reticulocyte counts and a significant positive correlation of plasma cell-free haemoglobin with protein carbonyl and nitrotyrosine levels. The obtained data shows that increased haemolysis in SCD increases plasma protein oxidation and nitration. © 2012 Informa UK, Ltd. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This work was supported by a grant (No: 2010.01.0103.007) from Akdeniz University Research Foundation.

Circumcision is the oldest and most frequent surgical procedure in the world and especially in Turkey as is seen in the other Islamic countries because of religious and traditional pressures. In this study, we aim to report the experience of circumcision at Cukurova University in a total of 76 patients with haemophilia between 1990 and 2011. We retrospectively reviewed medical records of 69 haemophilia patients without inhibitors and seven haemophilia patients with inhibitors who had been circumcised. Before the year 2000, factor concentrates were given before and after circumcision for 6-7 days. After 2000, we used fibrin glue together with factor concentrates for only 3 days. By-passing agents were used for circumcision in haemophilia patients with inhibitors. Twelve of 69 patients without inhibitors were referred to our centre with bleeding after the circumcision before diagnosis of haemophilia. Nine of these twelve patients had severe life threatening bleeding and three of them had moderate bleeding. Sixty-four patients with haemophilia were circumcised in our centre under general anaesthesia except for three patients who were given local anaesthesia. Thirteen of 57 haemophilia patients (22.8%) without inhibitors had seven mild and six moderate bleeding complications. A few patients had significant bleeding, despite adequate factor replacement. Five of seven haemophilia patients with inhibitors had two moderate and three mild bleeding complications. Our experience showed that circumcision for patients with haemophilia should be carefully performed by surgeons together with paediatric haematologist, under appropriate conditions in haemophilia centres which has comprehensive coagulation lab.

GI perforation after stem cell transplantation is extremely rare and is associated with poor prognosis. In addition, the clinical limitations of MMF are associated with GI intolerance and hematologic suppression. However, the exact mechanism whereby MMF induces changes in GI mucosa is unknown. Currently, there is no definite method to distinguish between GI toxicity associated with MMF and GVHD. It is important to recognize association between MMF and the histologic changes mimicking GVHD, given that GVHD is a significant differential diagnosis in stem cell transplant patients. MMF-induced colitis and GI perforation are extremely rare but should be considered in patients presenting with diarrhea and abdominal pain. Histology and clinical features are helpful to distinguish this condition from ischemic colitis. Early recognition of GI perforation is necessary for proper diagnosis and subsequent intervention. Emergency medical treatment and laparotomy have been shown to reduce the risk of fatal complications in patients presenting with GI symptoms suspected of GI perforation.

PubMedID: 18838398 The literature on the use of recombinant factor VIIa (rFVIIa), which was initially used in hemophiliac patients with inhibitors, for hemorrhages that cannot be managed with conventional methods or operations that cannot be performed safely is increasingly growing. This study presents a group of nonhemophiliac patients with hemorrhagic problems or hemorrhage risk for some interventions that were successfully resolved with the use of rFVIIa. The patient group was composed of 20 patients with different disorders resulting in similar results as hemorrhage or hemorrhage risk. Most of the patients were diagnosed with liver disorders primary or secondary to other diseases. The remaining cases were patients with leukemia, sepsis, intracranial hemorrhage, and burn. Some of the patients had multiple problems like a patient with liver disorder and intracranial hemorrhage or a leukemia patient with sepsis and disseminated intravascular coagulation. rFVIIa had been administered to the patients at dosages between 70 and 150 µg/kg up to 6 doses with 2-hour to 3-hour intervals. All the patients had benefited from the use of rFVIIa even though some of them died because of primary disease. This study shows that rFVIIa can be safely used in high-risk patients with a history of recurrent hemorrhage, for whom no improvement can be achieved in the hemostasis tests.

Tümör nekroze edici faktör(TNF) ilişkili apopitoz indükleyici protein (TRAIL) TNF süper ailesinin bir üyesidir. TRAIL pek çok organda ekprese edilen, hücre yüzeyinde yer alan transmembran bir proteindir. C-domainin (hücre dışında yer alan)ayrılması sonucunda serumda bulunan formunun oluşmasına izin verir.TRAIL, reseptörlerinden TRAIL reseptör 1 (TRAIL-R1) ve TRAIL reseptör 2 (TRAIL-R2)' ye bağlanarak apopitozu indükler bununla birlikte apopitoz sinyali TRAIL reseptör 3 (TRAIL-R3) ve TRAIL reseptör 4 (TRAIL-R4) ile bağlanması sonucunda indüklenemez. Apopitotik yolak bozuklukları ve lösemi gelişimi arasındaki ilişkiyi araştıran pek çok çalışma yapılmıştır.Çalışmamızda akut lösemi hastalarında ilk tanı anında serum TRAIL miktarını tespit etmek istedik. Serum TRAIL'ın akut lösemi hastalarında hasta sağkalımı ve klinik parametrelerle ilişkisini incelemeyi amaçladık. Materyal ve Metod: Bu çalışma Ekim 2009- Temmuz 2010 tarihleri arasında Çukurova Üniversitesi Tıp Fakültesi Çocuk Hematoloji ve Çocuk Onkoloji Bilim Dalına başvuran hastalarda yapıldı. Çalışmaya 9 ay-12 yaş 8ay yaş dağılımında yeni tanı almış 23 akut lenfoblastik lösemili (ALL) hasta ile, 9 gün-19 yaş dağılımında yeni tanı almış 14 akut miyeloblastik lösemili (AML) hasta dahil edildi. Sağlıklı, kan hastalığı olmayan, lösemi grubuna benzer yaş ve cinsiyetteki 21 çocuk, kontrol grubu olarak seçildi. Serum TRAIL düzeyleri Elisa yöntemi ile araştırıldı. Bulgular: Akut lösemi tanılı hastalar ile kontrol grubu karşılaştırıldığında akut lösemi hastalarında ortalama serum TRAIL düzeyi sağlıklı kontrollerden düşük tespit edildi (p=0,002). ALL'li yüksek risk grubundaki (HRG) hastalarda, TRAIL düzeyi kontrol grubuna göre düşük tespit edildi (p=0,008). Common akut lenfoblastik lösemi antijeni (CALLA )(-) B ALL grubunda TRAIL düzeyi kontrol grubuna göre düşük tespit edildi (p=0,004). Lösemi tanısı alan ve eksitus olan hastalarla yaşayan hastalar kıyaslandığında TRAIL düzeyi eksitus olan grupta düşük tespit edildi (p=0,004). Sonuç: Serum TRAIL lösemi hastalarında lökomogenezde rol oynayabilir. Hastalarımızda tespit edilen düşük serum TRAIL düzeyleri azalmış TRAIL aracılıklı apopitoza ve lökomogeneze neden olmuş olabilir. Akut lösemi patogenezinde serum TRAIL'ın rol aldığını önermek için eş zamanlı bakılmış TRAIL aracılıklı apopitotik aktivitenin ölçülmesi gereklidir.Düşük serum TRAIL düzeyi kötü prognozu gösteren bir belirteç olarak kullanılabilir. Daha kapsamlı sonuçlar elde etmek için daha çok sayıda vaka ile yapılmış prospektif çalışmalara ihtiyaç vardır Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a TNF superfamily member. TRAIL is transmembrane protein expressed on cell surfaces and has a broad expression pattern in a variety of organs. Cleavage of its C-terminal part (extracellular domain) allows for a soluble form of TRAIL.TRAIL induces apoptosis with its receptors TRAIL-receptor 1 (TRAIL-R1), TRAIL-receptor 2 (TRAIL-R2) however apoptosis can not be induced by receptors TRAIL-receptor 3 (TRAIL-R3) and TRAIL-receptor 4 (TRAIL-R4). There are many trials to search the correlation between leukemia and apoptotic pathway disorders. In this study we determined the seum levels of TRAIL in acute childhood leukemias at first diagnose. We aimed to determine the relation between the levels of serum TRAIL and patient's survey, clinical parameters. Material and Methods: The study was performed in patients admitted to Pediatric Hematology and Pediatric Oncology Department of Çukurova University Medical Faculty between October 2009 and July 2010. Twenty-three cases with new diagnosis acute lymphoblastic leukemia (ALL) at the age disturbition 9-months-12-year and 8-months and fourteen cases with new diagnosis acute myeloblastic leukemia (AML) at the age disturbition of 9 days-18 years are included in this study. Twenty-one healty children with no blood disease with similar sex and age with leukemia group was chosen as the control group. Serum TRAIL levels were determined by using ELISA method. Results: The comparison of the average values of the TRAIL levels in acute leukemia patients and control group have shown that patients with leukemia have low serum TRAIL levels (p=0.002). In patients with high-risk-grade (HRG) of ALL compared with control group have shown low serum TRAIL levels in HRG of ALL (p=0.008). In patients with common acute lymphoblastic leukemia antigen(CALLA)(- ) B ALL compared with control group have shown low serum TRAIL levels in CALLA(-) B ALL (p=0.004). Children with acute leukemias (ALL, AML) who died during treatment compared with survived group have shown low levels of serum TRAIL in expired patients (p=0.004). Conclusion: As a result, serum TRAIL might play a role in leukomegenesis. The low levels of serum TRAIL detected in our patients may be associated with leukomogenezis and impaired TRAIL-mediated apoptosis. To suggest soluble TRAIL's role in acute leukemias detection of TRAIL-mediated apoptosis is needed. The low serum TRAIL may be used as a sign of bad prognosis. For more comphrensive results prospective studies with greaater number of patients are needed

PubMedID: 14653399 Background: Granulocytic sarcoma (GS) is an uncommon extramedullary tumor composed of dense aggregates of immature myeloid precursor cells, which is usually associated with acute or chronic myeloid leukemia. The tumor may also be a predecessor to acute myeloid leukemia (AML). It may be found in any location throughout the body; however, intraoral occurrence is extremely rare. This report describes a case of gingival granulocytic sarcoma that developed prior to AML in a 12-year-old female. Methods and Results: The patient, who had a 3-month history of gingival enlargement, was diagnosed as having granulocytic sarcoma based on clinical, radiological, and histological findings. Although the tumor regressed significantly after two induction chemotherapy courses, the patient subsequently died due to pneumococcal sepsis and pleurisy. Conclusion: This case report affirms the importance of granulocytic sarcoma in the differential diagnosis of gingival enlargements, since the tumor may occur before bone marrow involvement by leukemic cells.

Background: In vitro studies have shown that nonionic radiographic contrast material may induce the generation of thrombin in blood, whereas ionic contrast agents, such as iohexol, do not. However, knowledge of the effects of contrast material on coagulation and fibrinolytic systems in vivo is limited. Objective: This study was designed to assess the effects of the nonionic radiographic contrast material iopamidol on hemostasis in patients undergoing coronary angiography or cardiac catheterization. Methods: Patients aged ?18 years with chest pain and/or dyspnea who underwent coronary angiography or cardiac catheterization with intra-arterial contrast material were assessed for hemostasis. Blood samples were drawn before and 3 minutes after injection of iopamidol. Complete blood count and coagulation profile (bleeding time, clotting time, clot retraction time, euglobulin lysis time [ELT], prothrombin and partial thromboplastin times, coagulation factor I [CFI] level, and platelet factor 3 [PF-3] availability) were assessed. The natural coagulation inhibitors protein C, protein S, and antithrombin III (AT-III) also were measured. Results: Thirty patients (7 males, 23 females; mean [SD] age, 51.3 [20.2] years; range, 17-79 years) were included in this single-center study. All hematologic variables (hemoglobin, white blood cell count, and platelet count) decreased significantly (P < 0.001, P < 0.001, and P < 0.05, respectively) after administration of iopamidol but remained within normal limits. Mean levels of protein C, protein S, and AT-III did not change significantly after administration of iopamidol. Bleeding time was not changed significantly, and PF-3 availability was prolonged in both groups, but the changes were not statistically significant. Conclusions: In this study population, although hemostasis remained grossly intact after injection of nonionic contrast material, the coagulation system may have been affected by the accelerated consumption of CFI and platelets. The affected variables were platelets, clot retraction time, ELT, and natural coagulation inhibitors (protein C, protein S, and AT-III). Although the natural coagulation inhibitors remained within the normal range, the correlations were found significant. These changes in hemostasis affected the vascular phase. If the vascular compartment, especially the endothelium, remained intact, the infusion of nonionic agents in low concentrations might be safe for angiography and other procedures; however, more studies are needed. Copyright © 2003 Excerpta Medica, Inc.

PubMedID: 12747461 Background: The purpose of this case report is to present severe alveolar bone destruction and gingival enlargement as initial manifestation of Burkitt cell type acute lymphoblastic leukemia (ALL-L3) in a 14-year-old boy. Methods: The patient was referred to the periodontology department with a 4-week history of gingival enlargement and loosening of teeth. The clinical examination revealed gingival enlargement and expansion of alveolar mucosa particularly in molar regions of both jaws. Almost all teeth had deep periodontal pockets and severe mobility. While the radiographs showed severe alveolar bone loss which extended to apical thirds of many teeth, the microbiologic analysis revealed that the patient did not harbor major periodontopathogenic bacteria species. The results of blood tests and bone marrow aspiration were compatible with ALL-L3. Results: Remission-induction treatment with BFM-90 ALL chemotherapy protocol was started; however, the patient died 4 weeks after the diagnosis due to neutropenic sepsis. Conclusions: Although no biopsy was performed, it is possible that the severe periodontal destruction and gingival enlargement in this case may have been due to the infiltration of leukemic cells in gingiva, periodontal ligament, and alveolar bone. The similarities of these findings with numb chin syndrome (NCS) and Burkitt's lymphoma (BL) are discussed in this report.

PubMedID: 22057265 A 4-year-old girl presented with fever, coughing, and vomiting; followed by unconsciousness. Magnetic resonance imaging showed hyperintense changes in the thalami bilaterally, brain stem, cerebellum, and subcortical cortex. Novel influenza A (H1N1) virus was identified by polymerase chain reaction in patient's nasopharyngeal swab specimen. We reported a rare case of clinically severe, novel influenza A-associated encephalitis. Novel influenza A should be considered in the differential diagnosis in patients with seizures and mental status changes, especially during an influenza outbreak. © 2011 Springer-Verlag.

Amaç: Hemofili tekrarlayan kanama ataklarına sekonder olarak kas- iskelet sorunlarına neden olmaktadır. Bu çalışmada, su içi egzersizlerinin, kas ve eklem problemleri olan şiddetli hemofili A hastalarında etkilerinin araştırılması amaçlanmıştır. Materyal ve Metod: Proflaksi alan, şiddetli hemofili A hastası (n=11) düzenli olarak egzersiz uygulamasına alınmıştır. Bulgular: Çalışmaya katılan hastaların, sağ bacaklarında üst bacak, orta bacak ve calf çevrelerinde (42.0 ± 2.4, 43.0 ±2.1 ; 37.1 ±1.9, 39.0 ±1.8; 28.1 ± 1.4, 28.9 ±1.3 respectively) (mean ± SE), sol bacaklarında üst ve orta bacak çevrelerinde (36.9 ± 1.5 , 38.9 ± 1.5 ; 41.2 ± 2.2 , 42.9 ± 2) egzersiz öncesi değerlerine göre istatistiksel olarak anlamlı farklılık bulunmuştur (p

PubMedID: 24533957 [No abstract available]

MikroRNA'lar, genom üzerinde protein kodlayan intron veya ekzon bölgeleri ve protein kodlamayan bölgelerdeki RNA genlerinden transkripsiyonu sağlanan, fakat proteine translasyonu gerçekleşmeyen, fonksiyonel RNA molekülleridir. MikroRNA’lar protein translasyonunun inhibisyonuna ve/veya mRNA'nın yıkımına neden olur. Yapılan çoğu çalışmada bu küçük moleküllerin hematopoezde farklılaşma, çoğalma ve apopitoz gibi çok önemli hücresel olaylarda kritik öneme sahip olduğunu göstermiştir. Malign hastalıklardaki rolü giderek daha fazla araştırmanın konusu olmaktadır. MikroRNA’lar bir ya da birden fazla hedef geni baskılayarak hücrenin gelişim, farklılaşma, çoğalma, ölümü gibi farklı olaylarda rol oynarlar. miRNA genlerinin %50'sinden fazlası kanser ile ilişkilendirilmiş genom üerinde bulunur. Yapılan çok sayıda deneysel çalışma; miRNA'ların yeni bir onkogen veya tümör baskılayıcı gen sınıfı oluşturabileceğini göstermiştir. Normal ve patolojik dokular arasında farklı seviyede ifade edilen miRNA'lar tespit edilerek, insan kanserlerinde tanı ve tedavide etkili olabilecek yeni miRNA'lar belirlenebilecektir. Mikro-RNAs are functional, non-protein coding RNA molecules and their transcriptions provided by intron or exon regions of the genome and non-protein coding regions of RNA genes. Mikro-RNAs inhibit translation of protein and / or cause destruction of mRNA. Most of studies have demonstrated that many of these small molecules have critical importance in many important cellular events such as hematopoiesis, differentiation, proliferation and apoptosis. The role of mikro-RNAs in malign diseases have become the subject of research increasingly. Mikro-RNAs play a role in different events such as cell growth, differentiation, proliferation and death by suppressing one or more target gene. More than 50% of miRNA genes are located on the genome which has associated with cancer. A large number of experimental studies show that miRNAs may have generate a new class of oncogenes or tumor suppressor gene. MiRNAs are thought to be identified at a different level of expression in normal and pathological tissues can be determined between the miRNAs that are effective diagnosis and treatment of human cancers.

PubMedID: 16476096 [No abstract available]

Abstract 5169 Introduction Management of hemoglobinopathies, mainly beta-thalassemia major, is well studied at controlled clinical trials. However, one should keep in mind that real life experience of pediatric patients with thalassemia major show remarkable differences across geographies and social-economic status. The effect of iron overload (IO) and outcome of chelation therapy also vary widely in this population. Chelators differ in side-effect profile, tolerability and ease of adherence, and (to some degree) efficacy for any specific patient. The aim of the present study was to determine the characteristics of children with hemoglobinopathies receiving oral iron chelators (OICs) in the treatment of transfusional IO and to evaluate treatment outcomes, adverse events, and growth and sexual development of these children after 3 years follow-up period. Method In this prospective, multi-center, non-interventional study, patients with 2–18 years of age with hemoglobinopathies and transfusional IO who were on or began to receive oral ICT were enrolled. Four hundred patients were planned to be included and followed for 3 years. The clinical and demographic characteristics of the patients, comorbidities, type and dosage of oral ICT, laboratory results related to IO markers, imaging results and serious adverse events were recorded. Results Four hundred ninety-two patients from 30 centers representing the Turkish patient's profiles were enrolled. This was the baseline analyses of 429 patients, of whom 407 had a primary diagnosis of beta-thalassemia major, and 22 had a primary diagnosis of sickle cell anemia (homozygous). Data about growth and sexual development were also collected and will be reported according to age groups and treatment history. The characteristics of the patients are summarized in Table 1. The type and dosage of current oral ICT and ICT history are presented in Table 2. Discussion To our knowledge this is the largest prospective study in pediatric patients diagnosed with hemoglobinopathies, particularly thalassemia major, and treated with OICs due to IO caused by regular transfusions. In this analysis, we reported baseline characteristics of this pediatric cohort. It is noteworthy to report that the pretransfusion hemoglobin levels of the majority (226 of 405 patients) of the thalassemic cohort were under 9 g/dL, suggesting a suboptimal transfusion regimen. IO was followed mainly with serum ferritin (SF) levels and many patients were not monitored for cardiac or liver IO. Of 429 patients, 339 were enrolled with IO (SF>1000 ng/mL), suggesting a non effective ICT history. Of 25 beta thalassemia patients who were treated with deferiprone (DFP), 22 had SF>1000 ng/mL (mean: 2918. 31±1477. 08). The maximum dose of deferasirox (DFX) was limited by health authority to 30 mg/kg/day during the first 6 months of the 1-year enrollment period. The mean dose of DFX for the patients with SF levels >1000 ng/mL and who were treated with DFX with a dose of ≤30 mg/kg/day was 25. 38±5. 03 mg/kg/day, suggesting a suboptimal dosing for a negative iron balance. This may be one of the reasons of the high mean SF level at baseline. Moreover, the treatment duration with OICs and effectiveness of previous treatment varied. The results of this study will reflect real life experience and help us to understand obstacles in the management of IO in this patient population. Disclosures: Antmen: Novartis Oncology: Speakers Bureau. Organ:Novartis Oncology: Employment. Canatar:Novartis Oncology: Employment. Koseoglu:Novartis Oncology: Consultancy.

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Background We conducted an investigator-driven, multicenter, open label, randomized study to establish whether the source of factor VIII (FVIII) replacement (plasma-derived, pd; or recombinant, r) affects the rate of inhibitory alloantibodies in previously untreated patients (PUPs) with severe hemophilia A. Methods Between 2010 and 2014, 303 PUPs who provided consent through their tutors were screened at 42 participating sites in 14 countries from Africa, the Americas, Asia and Europe. The original aim was to screen 300 patients, randomize 270 (10% screening failure) and follow them for 50 exposure days (ED) or 3 years. Once the intended numbers were included, follow-up was terminated due to logistic and budgetary reasons. Screening criteria were age 5 BU/ml) were a secondary outcome. Patients were censored at the end of the follow-up (50 EDs, 3 years or study end), at inhibitor development or drop-out. Kaplan-Meier and Cox regression survival analyses took into account as putative confounders FVIII gene mutations, ethnicity, hemophilia and inhibitor family history, previous blood component exposure, therapeutic regimen, age at first treatment and country site. Results Of 303 screened patients, 39 were screening failures, and 13 were excluded because 3 patients had received >5 treatments with blood components and 10 were not infused after randomization. The remaining 251 patients were analysed and 35 had truncated follow-up (25 dropout, 10 study termination). Patients were aged 0-81 months at randomization (median 14 months) and received between 1 and 50 infusions of FVIII concentrates (median 22). Of those who did not develop an inhibitor, over 70% had >20 ED. 76 patients developed an inhibitor, of which 50 were high-titred. The cumulative inhibitor incidence was 35.4% (95% confidence interval (CI95) 28.9-41.9%). 90% of inhibitors developed within 20 EDs, both for all and high-titre inhibitors. After randomization 125 patients received pdFVIII and 126 rFVIII. The putative confounders were equally divided between the two product class arms. There were 29 inhibitors (20 high-titred) in the group treated with the class of pdFVIII and 47 (30 high-titred) in those treated with rFVIII. The cumulative inhibitor incidence was 26.7% (CI95 18.3-35.1%) for pdFVIII and 44.5% (CI95 34.7-54.3%) for rFVIII (Figure). For high-titre inhibitors the cumulative incidence was 18.5% (CI95 12.1-26.9%) for pdFVIII and 28.4% (CI95 19.6-37.2%) for rFVIII. By univariate Cox regression analysis rFVIII was associated with an 87% higher incidence of inhibitors than pdFVIII (hazard ratio (HR) 1.87, CI95 1.18-2.97). For high-titre inhibitors the rate was 70% increased (HR 1.70, CI95 0.96-2.99). The associations did not materially change after adjustment for putative confounders: in adjusted models the rate remained 70-90% elevated for rFVIII vs pdFVIII. When analysis was restricted to sites that had not randomized patients to a second generation full length rFVIII or pdFVIII (n=131 patients, 25 inhibitors), the risk of other rFVIII concentrates vs pdFVIII was still twofold increased (HR 1.99, CI95 1.00-3.99). Conclusions The rFVIII product class was associated with a 1.87-fold higher incidence of inhibitors than the pdFVIII class. This difference remained even when second generation full length rFVIII concentrate was excluded from the analyses. The results of this randomized study have implications in the choice of product for management of PUPs, as inhibitor development remains a major challenge in the management of haemophilia A. (Funded by the Angelo Bianchi Bonomi Foundation, Italian Ministry of Health, Grifols, Kedrion and LFB - Registed at EudraCT 2009-001186-88). Figure 1. Figure 1. Disclosures Peyvandi: Octapharma: Other: Investigator; LFB, Kedrion, Novonordisk, Bayer, Roche, CSL Behring.: Consultancy, Honoraria, Research Funding. Mannucci:Novonordisk, Grifols, Kedrion, Bayer, Biotest, Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Karimi:Octapharma: Other: Investigator. Young:Baxter, Grifols: Consultancy, Honoraria. Santagostino:Roche: Speakers Bureau; Bayer: Speakers Bureau; Baxter/Baxalta: Speakers Bureau; Octapharma: Speakers Bureau; Biotest: Speakers Bureau; Novo Nordisk: Speakers Bureau; Kedrion: Speakers Bureau; Biogen/Sobi: Speakers Bureau; CSL Behring: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau. Mancuso:Baxter, Pfizer, CSL Behring, Baxter, Sobi/Biotest: Consultancy; Novo Nordisk, Bayer: Speakers Bureau. Mahlangu:Biogen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Research Funding; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bonanad:Baxalta: Research Funding. Ewing:Baxter, Novo Nordisk, Grifols, Bayer, Kedrion: Honoraria. Owaidah:King abdulaziz city for science, Novo Nordisk, Bayer: Honoraria, Research Funding. Kobrinsky:Octapharma: Speakers Bureau; CSL Behring: Speakers Bureau; Sanofi: Speakers Bureau; Kedrion Biopharma: Membership on an entity's Board of Directors or advisory committees. Kavakli:Baxter: Other: advisory board member and received educational and investigational support; Bayer: Other: advisory board member and received educational and investigational support; Novo Nordisk: Other: advisory board member and received educational and investigational support; Pfizer: Other: advisory board member and received educational and investigational support; Bio Products Laboratory: Other: received educational and investigational support; CSL Behring: Other: received educational and investigational support; Octapharma: Other: received educational and investigational support. Manco-Johnson:Baxter, bayer, biogen, CSL Behring, NovoNordish: Honoraria. Neme:Novo Nordisk and Pfizer: Other: fees for speaking. Wicklund:NovoNordisk, Bayer, Baxter (now Baxalta), Biogen-Idec, CSL-Behring, National Hemophilia Foundation: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zulfikar:Eczacýbaþý-Baxter, Pfizer, Novo Nordisk: Consultancy, Honoraria, Research Funding.

Angiogenesis has been associated with the growth, dissemination and metastasis and has been shown to be a prognostic. Although there are some data suggesting that angiogenesis may have a role in the pathophysiology of leukemia, its role in patient prognosis is yet to be defined. We analyzed the expression level of vascular endothelial growth factor (VEGF), an angiogenesis promoter and its possible- prognostic value in bone marrow samples at the time of diagnosis and remission of acute childhood leukemia patients. Besides 46 patients diagnosed as ALL or AML, 16 children were also included as a control group in the study. Our data have demonstrated that VEGF levels of AML patients were found higher than the control group statistically (P = 0.022). However we could not find any significant difference between VEGF levels of diagnosis and remission in both AML and ALL groups by blastic VEGF expression (P > 0.05). In this study the higher levels of VEGF in AML patients is one of the main findings although we were not able to assess any role of VEGF in predicting prognosis in pediatric leukemia patients by evaluating blastic cell VEGF expression. These results have demonstrated that the relationship between angiogenesis or angiogenesis promoters and hematological malignancies is not clear and simple as different methods or different cells beside different angiogenesis promotors are involved to these studies. So that not only tumor cells and their cytokines but also surrounding cells and their cytokines must be taken into consideration with the standardized study methods in the further studies to obtain a promising treatment approach. © 2011 Indian Society of Haematology & Transfusion Medicine.

BACKGROUND: Patients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease. Effective strategies to prevent bleeding in such patients have not yet been established. METHODS: We enrolled patients with hemophilia A who were older than 2 years of age, had high-titer inhibitors, and used concentrates known as bypassing agents for bleeding in a prospective, randomized, crossover study comparing 6 months of anti-inhibitor coagulant complex (AICC), infused prophylactically at a target dose of 85 U per kilogram of body weight (±15%) on 3 nonconsecutive days per week, with 6 months of on-demand therapy (AICC at a target dose of 85 U per kilogram [±15%] used for bleeding episodes). The two treatment periods were separated by a 3-month washout period, during which patients received on-demand therapy for bleeding. The primary outcome was the number of bleeding episodes during each 6-month treatment period. RESULTS: Thirty-four patients underwent randomization; 26 patients completed both treatment periods and could be evaluated per protocol for the efficacy analysis. As compared with on-demand therapy, prophylaxis was associated with a 62% reduction in all bleeding episodes (P

PubMedID: 20088956 Development of inhibitors to infused factor concentrates represents a major clinical and economic challenge in the treatment of haemophilic patients. It has been shown that a delay in initiation of treatment leads to requirement of a larger number of injections to stop the bleeding but this has never been formally linked to costs associated with the bleeding. The objectives of this study were to assess the relationship between time to initiation of NovoSeven® and total costs, number of doses administered and time to bleeding resolution in mild to moderate bleeding episodes. Data on time to treatment initiation, time to bleeding resolution and on all resource use related to the bleeding were extracted from medical records in Turkey for 129 bleeding episodes. Regression analysis was used to assess the impact of time to treatment on outcomes. Longer time to treatment initiation increased both total costs associated with the bleeding, the number of doses needed and the time to bleeding resolution. Treatment in hospital was associated with significantly longer time to treatment, higher costs and longer time to bleeding resolution as compared with home treatment or outpatient treatment. When controlling for other bleeding characteristics, the cost of bleedings treated in hospital was more than 150% higher. This study shows that treatment with NovoSeven® should be initiated as soon as possible after the onset of bleeding in order to minimize costs and optimize outcomes. Home treatment reduces time to treatment initiation and also reduces costs related to the bleeding. © 2010 Blackwell Publishing Ltd.

Amac: Tumor nekroze edici faktor(TNF) iliskili apopitoz indukleyici protein (TRAIL) TNF super ailesinin bir uyesidir. TRAIL pek cok organda ekprese edilen, hucre yuzeyinde yer alan transmembran bir proteindir. C-domainin (hucre disinda yer alan)ayrilmasi sonucunda serumda bulunan formunun olusmasina izin verir.TRAIL, reseptorlerinden TRAIL reseptor 1 (TRAIL-R1) ve TRAIL reseptor 2 (TRAIL-R2)' ye baglanarak apopitozu indukler bununla birlikte apopitoz sinyali TRAIL reseptor 3 (TRAIL-R3) ve TRAIL reseptor 4 (TRAIL-R4) ile baglanmasi sonucunda induklenemez. Apopitotik yolak bozukluklari ve losemi gelisimi arasindaki iliskiyi arastiran pek cok calisma yapilmistir.Calismamizda akut losemi hastalarinda ilk tani aninda serum TRAIL miktarini tespit etmek istedik. Serum TRAIL'in akut losemi hastalarinda hasta sagkalimi ve klinik parametrelerle iliskisini incelemeyi amacladik. Materyal ve Metod: Bu calisma Ekim 2009– Temmuz 2010 tarihleri arasinda Cukurova Universitesi Tip Fakultesi Cocuk Hematoloji ve Cocuk Onkoloji Bilim Dalina basvuran hastalarda yapildi. Calismaya 9 ay-12 yas 8ay yas dagiliminda yeni tani almis 23 akut lenfoblastik losemili (ALL) hasta ile, 9 gun-19 yas dagiliminda yeni tani almis 14 akut miyeloblastik losemili (AML) hasta dahil edildi. Saglikli, kan hastaligi olmayan, losemi grubuna benzer yas ve cinsiyetteki 21 cocuk, kontrol grubu olarak secildi. Serum TRAIL duzeyleri Elisa yontemi ile arastirildi. Bulgular: Akut losemi tanili hastalar ile kontrol grubu karsilastirildiginda akut losemi hastalarinda ortalama serum TRAIL duzeyi saglikli kontrollerden dusuk tespit edildi (p=0,002). ALL’li yuksek risk grubundaki (HRG) hastalarda, TRAIL duzeyi kontrol grubuna gore dusuk tespit edildi (p=0,008). Common akut lenfoblastik losemi antijeni (CALLA )(-) B ALL grubunda TRAIL duzeyi kontrol grubuna gore dusuk tespit edildi (p=0,004). Losemi tanisi alan ve eksitus olan hastalarla yasayan hastalar kiyaslandiginda TRAIL duzeyi eksitus olan grupta dusuk tespit edildi (p=0,004). Sonuc: Serum TRAIL losemi hastalarinda lokomogenezde rol oynayabilir. Hastalarimizda tespit edilen dusuk serum TRAIL duzeyleri azalmis TRAIL aracilikli apopitoza ve lokomogeneze neden olmus olabilir. Akut losemi patogenezinde serum TRAIL'in rol aldigini onermek icin es zamanli bakilmis TRAIL aracilikli apopitotik aktivitenin olculmesi gereklidir.Dusuk serum TRAIL duzeyi kotu prognozu gosteren bir belirtec olarak kullanilabilir. Daha kapsamli sonuclar elde etmek icin daha cok sayida vaka ile yapilmis prospektif calismalara ihtiyac vardir.

PubMedID: 18206400 Objective: In systemic sclerosis (SSC), certain abnormalities can occur in fibroblasts, endothelial cells, and immune system cells. Severe pathological changes such as visceral fibrosis and obliteration of the lumen of arteries may develop due to functional alterations of these cells. Because the vascular abnormality is a central mechanism of sclerosis, the aim of this study was to further investigate the impaired vascularity in the gingival tissues of SSC patients by means of immunohistochemistry using vascular endothelial growth factor A (VEGF-A), VEGF-C, and CD34 staining. Study design: Thirteen SSC patients and 11 systemically healthy controls who had moderate gingivitis were included in the study. Gingival biopsies were obtained from the interdental papilla, and VEGF-A, VEGF-C, and CD34 analyses were done by using immunohistochemical methods. Results: Patients with scleroderma had higher levels of inflammatory infiltrate (P = .041) and microvessel density (P = .003) in their gingival biopsy samples. In contrast, when compared with the controls, the expressions of VEGF-A and VEGF-C were significantly lower in scleroderma patients (P = .033 and P = .015, respectively). Conclusion: These findings may reflect the defective vascularity and the pronounced histological inflammation of the gingival tissues in systemic scleroderma and may provide a novel target for treatment methods for the gingival involvement in these patients. © 2008 Mosby, Inc. All rights reserved.

PubMedID: 16728364 Mucormycosis is an uncommon, severe, life-threatening fungal infection in the immunocompromised host. Mucormycosis with aplastic anemia is seen rarely. Only a few cases of cardiac mucormycosis with aplastic anemia have been reported in the literature. The authors present a case with severe aplastic anemia that did not respond to classic and immunosuppressive treatment for disease and developing invasive cardiac mucormycosis despite empiric treatment for febrile neutropenia. Copyright © Taylor & Francis Group, LLC.

Osteopetrosis, also known as marble bone disease, is a rare in which osteoclast dysfunction causes defective bone resorption and increased bone mass. This disease has been classified into four types. The most severe and rare form is infantile malignant osteopetrosis. So we reported and discussed two siblings patients with infantile malignant osteopetrosis with new knowledge in the literature. Osteopetrosis, also known as marble bone disease, is a rare in which osteoclast dysfunction causes defective bone resorption and increased bone mass. This disease has been classified into four types. The most severe and rare form is infantile malignant osteopetrosis. So we reported and discussed two siblings patients with infantile malignant osteopetrosis with new knowledge in the literature.

Sickle cell anemia is a chronic hemolytic anemia with vasoocclusive crisis and is the most common symptomatic event that causes tissue hypoxia in many systems. Pulmonary crisis is one of them and its the major cause of mortality and morbidity in sickle cell anemia. Furthermore, pulmonary crisis is the second clinical situation for hospitalization. Pneumoia must be thought in differential diagnosis and is too difficult to rule out. Two cases with pulmonary crises with sickle cell anemia were presented with up to date knowledge. Sickle cell anemia is a chronic hemolytic anemia with vasoocclusive crisis and is the most common symptomatic event that causes tissue hypoxia in many systems. Pulmonary crisis is one of them and its the major cause of mortality and morbidity in sickle cell anemia. Furthermore, pulmonary crisis is the second clinical situation for hospitalization. Pneumoia must be thought in differential diagnosis and is too difficult to rule out. Two cases with pulmonary crises with sickle cell anemia were presented with up to date knowledge.

Objective: Coagulopathy resulting from liver pathologies and the hemorrhages secondary to this are the complications observed in chronic liver diseases, fulminant hepatitis, hepatocellular cancer, liver transplantation and other similar conditions. The literature on the use of rFVIIa which was initially used in hemophiliac patients with inhibitors for hemorrhages that can not be managed with conventional methods or operations that can not be performed safely, is increasingly growing. Here we will present a patient that was successfully operated by using rFVIIa for recurrent intracranial hemorrhage secondary to liver disease. Case: The 7 months old female infant was brought to our clinic due to abdominal distention and bleeding from anus. Her medical history included a treatment by hospitalization in the Regional Hospital when two months old due to high fever, forceful vomiting, foaming at mouth and yellow coloring of skin (convulsion?), operation due to hemorrhage detected at cerebral imaging, two subsequent operations at the same hospital due to hemorrhage upon sudden purple coloring of skin observed 1.5 months later and finally, dismission from hospital following a 25-day monitoring under conditions of intensive care. Following the yellow coloring of eyes, hematemesis, abdominal distention, echhymoses in the back and chest observed in the patient, she was referred to our clinic and her cerebral CT findings revealed pressure effect and subdural hematoma extending from temporal localization to frontoparietal cranium at left and to tentorium superior section and anterior interhemispheric fissure in cranium at posterior, with the widest part reaching 1.5 cm. The patient, for whom an operation was planned, was twice supplemented with platelet suspension at a dose of 10 cc/kg (53000/mm3) for her thrombocytopenia. Despite the administration of Frozen Plasma supplement, PT, PTT and Fibrinogen was detected as 18, 42.8 and 117 mg/dl, respectively and 1.2 mg of Novoseven was administered to the patient once preoperatively and twice postoperatively at a two-hour interval due to her history of postoperative hemorrhage. Upon the preoperative detection of PT, PTT, Fibrinogen as 12.1, 43.1 and 145 mg/dl and KZ and PZ as 6 and 5 minutes respectively, the patient was operated. No new postoperative hemorrhages or other complications were observed. The diagnosis of Gaucher disease was made at the bone marrow examination and the relevant treatment was planned. Conclusion: rFVIIa can be safely used in high-risk patients with a history of recurrent hemorrhage, for whom no improvement can be achieved in the hemostasis tests.

PubMedID: 15725319 Background: Invasive procedures such as bone marrow aspiration in children may be painful and cause anxiety. We investigated the efficacy and safety of remifentanil (R) alfentanil (A), remifentanil-midazolam (RM), and alfentanil-midazolam (AM) combinations in providing analgesia and sedation for bone marrow aspiration. Methods: Eighty children undergoing a diagnostic bone marrow aspiration whose ages ranged from 5-16 years (mean 9.20 ± 3.00 years) were enrolled in this study. The patients were randomly assigned to one of 4 treatment groups. Vital signs, sedation and pain scores, somatic responses (sweating and tears) were recorded before, during bone marrow aspiration and after 5 and 15 min of the procedure. Results: There were no statistical differences between sedation and the CHEOPS scores of the four groups during and after the procedures. The VAS scores were significantly higher for group A compared with groups R and RM during the procedure (P < 0.008). There were no differences between the VAS scores in group AM compared with groups R and RM (P > 0.008). There were also no statistical differences among the VAS scores of four groups after the procedure (P > 0.008). All patients had adequate sedation and analgesia. None of the patients in the study had deep sedation, hypotension, bradycardia, hypoxemia, or respiratory depression. Conclusions: Remifentanil, alfentanil, remifentanil-midazolam, and alfentanil-midazolam combinations are effective in children and can be used safely in bone marrow aspiration which is a brief but painful procedure performed in the pediatric patient group. © 2004 Blackwell Publishing Ltd.