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β‐thalassemia major is an inherited hemoglobinopathy that requires lifelong red blood cell transfusions and iron chelation therapy to prevent complications due to iron overload. Traditionally, β‐thalassemia has been more common in certain regions of the world such as the Mediterranean, Middle East, and Southeast Asia. However, the prevalence of β‐thalassemia is increasing in other regions, including Northern Europe and North America, primarily due to migration. This review summarizes the available data on the changing incidence and prevalence of β‐thalassemia as well as factors influencing disease frequency. The data suggest that the epidemiology of β‐thalassemia is changing: Migration has increased the prevalence of the disease in regions traditionally believed to have a low prevalence, while, at the same time, prevention and screening programs in endemic regions have reduced the number of affected individuals. Various approaches to prevention and screening have been used. Region‐specific prevention and treatment programs, customized to align with local healthcare resources and cultural values, have been effective in identifying patients and carriers and providing information and care. Significant challenges remain in universally implementing these programs.

Background: Proper clinical use of blood and blood products requires competent theoretical and practical knowledge of transfusion medicine. The Curriculum Development and Standard Determination System Medical Specialization Board is prepared Hematology Specialist Education Core Curriculum in Turkey. In this study, we aimed to determine the access of hematologists to the learning objectives defined by curriculum for the transfusion medicine and the factors affecting it.Methods: Hematologists who have been members of Turkish Hematology Society since 2013 have been included in the study, The survey questions were prepared based on the curriculum for transfusion medicine. The study was applied to hematologists with "survey monkey" application. The questionnaire consisted of a competence self-assessment with Likert scale and theoretical multiple-choice knowledge questions. Results: Of the 213 hematologists, 54 (25%) were included in the study. Hematologists rated their competences in the clinical competence areas as 3,65 ± 0,73 (median 3,60) as "I know but not t a sufficient level". The participants 'perception of competence was "I know, but not at a sufficient level'" with an average of 3.31 ± 0.84 (median3.5) in the blood banking field, while the average in hemapheresis and transfusion medicine was 4.04 ± 0.63 (median 4) as "enough". In interventional procedures, hematologists stated that their vocational competences were 2,79± 0,92 (median 2,93) on average as "I have an idea- I know, but not enough". The correct answer to 13 theoretical questions was an average of 6,96 ± 1,89 (median 7). Hematologists performing blood rotation felt significantly more competent than the physicians who could not do the rotation in the blood bank, blood banking t(52) = -3.9, p < .001 , transfusion medicine and interventional competence t(52) = -2.2, p = .04 . Physicians who believed that they are sufficient in the blood banking area, were more confident in transfusion medicine r(54) = .67, p

Aim: Mastocytosis is a rare disease characterized by clonal mast cell proliferation in one or more organs. It can lead to different clinical manifestations and has no definitive treatment. in this study, we aimed to evaluate the clinical and laboratory characteristics of our patients diagnosed with mastocytosis in our clinic. Materials and Methods: Thirteen patients that were followed up with the diagnosis of mastocytosis at the Pediatric Hematology Clinic, in the Ege University Faculty of Medicine between November 1999 and April 2016 were retrospectively analyzed. Results: Seven of patients were female (53.8%) and six were male (42.6%). the mean age at diagnosis was 20 (3-68) months. At the time of diagnosis, complete blood count and peripheral smear were found to be compatible with the anemia of iron deficiency in three patients. Other parameters were normal. Mean tryptase level was detected as 5.9 (3.6-16.6) ng/mL, and only one tryptase level was found as slightly increased. the median level of total IgE was 91.1 (4.47-362) IU/mL. Mast cell proliferation was not detected in bone marrow aspiration and biopsy material of any patients. All of the cases were evaluated as cutaneous type mastocytosis. Conclusion: the possibility of mastocytosis in systemic form in childhood is very rare and bone marrow examination may be necessary in selected cases.

[No Abstract Available], Novartis Pharmaceuticals Corporation, This study was sponsored and funded by Novartis Pharmaceuticals Corporation.

Monitoring liver and cardiac iron stores by magnetic resonance imaging (MRI) enables identifying patients at risk of organ-specific morbidity and better tailoring of iron chelation therapy in thalassemia. Nevertheless, serum ferritin (SF) remains the only tool for monitoring iron status in most resource-poor regions. In this study, we assessed the impact of using MRI techniques to guide iron chelation therapy on iron overload outcomes in a cohort of 99 patients with thalassemia major (TM, mean age at baselines 20.7 +/- 6.9 years) followed from 2006 to 2019. We also assessed the ability of SF trends to predict changes in consecutive liver iron concentration (LIC) and cardiac T2* (cT2*) measurements. The most commonly used chelator was deferasirox at baseline (65%) and final (72%) assessments. Overall, patients with safe LIC values (< 7 mg/g dw) increased from 57 to 77%, and safe cT2* values (> 20 ms) increased from 72 to 86%. We obtained the most significant improvement in patients with severe and moderate liver (p = 0.006 and p < 0.001) and cardiac (p < 0.0013 and p < 0.0001) iron overload at baseline. SF trends were in the same direction in 64% of changes in LIC, but only 42% of changes were proportional. Most of the changes in SF (64%) and LIC (61%) could not predict changes in cT2*. Moreover, downward trends in SF and LIC were associated with worsening cardiac iron in 29% and 23.5% of consecutive cT2* measurements. Liver and cardiac MRI-driven oral iron chelation improved the iron status of subjects with TM and demonstrated the importance of using validated MRI techniques in critical clinical decisions.

Introduction: Cytomegalovirus (CMV) infections in developing countries are experienced at an early age. This study was performed to investigate the frequency of reactivation and risk factors of infection acquired at an early age of nontransplant acute lymphoblastic leukemia (ALL) patients receiving immunosuppressive therapy with weekly monitoring of CMV levels in Turkey. Materials and Methods: This was a retrospective, single-center study of 172 pediatric patients (102 boys and 70 girls) with ALL. All patients were monitored routinely for CMV-DNA at the initial presentation of leukemia and twice a week during chemotherapy. The CMV immunoglobulin (Ig)M/IgG titers were measured at admission. Results: CMV seropositivity at baseline was 90,11%. The overall prevalence of CMV infection (viremia) was 70.34%, 116 of whom were seropositive for CMV IgG and 5 of whom were negative for CMV at the time of ALL diagnosis. Reactivation was more common than de novo CMV infections (P=0.000). CMV seropositivity at the beginning of the leukemia diagnosis was found to be an independent predictor for developing CMV infection (P=0.001). A total of 60 CMV infection episodes were treated with antivirals. Four of these included organ involvement. The duration of CMV-DNA viremia episodes was longer in patients with CMV-DNA >= 1000 copies/mL (n=45) than in those with lower CMV-DNA levels (P=0.002). Infection was shown not to be associated with chemotherapy phase. Conclusion: This study suggests the importance of monitoring for CMV infections in developing countries because of frequent reactivations in seropositive ALL patients. It should be kept in mind that low CMV-DNA levels may also lead to organ involvement.

WOS: 000478608100031, PubMed ID: 31148155, Transfusion-dependent thalassaemia (TDT) requires red blood cell concentrates (RBCC) to prevent complications of anaemia, but carries risk of infection. Pathogen reduction of RBCC offers potential to reduce infectious risk. We evaluated the efficacy and safety of pathogen-reduced (PR) Amustaline-Glutathione (A-GSH) RBCC for TDT. Patients were randomized to a blinded 2-period crossover treatment sequence for six transfusions over 8-10 months with Control and A-GSH-RBCC. The efficacy outcome utilized non-inferiority analysis with 90% power to detect a 15% difference in transfused haemoglobin (Hb), and the safety outcome was the incidence of antibodies to A-GSH-PR-RBCC. By intent to treat (80 patients), 12 center dot 5 +/- 1 center dot 9 RBCC were transfused in each period. Storage durations of A-GSH and C-RBCC were similar (8 center dot 9 days). Mean A-GSH-RBCC transfused Hb (g/kg/day) was not inferior to Control (0 center dot 113 +/- 0 center dot 04 vs. 0 center dot 111 +/- 0 center dot 04, P = 0 center dot 373, paired t-test). The upper bound of the one-sided 95% confidence interval for the treatment difference from the mixed effects model was 0 center dot 005 g/kg/day, within a non-inferiority margin of 0 center dot 017 g/kg/day. A-GSH-RBCC mean pre-transfusion Hb levels declined by 6 center dot 0 g/l. No antibodies to A-GSH-RBCC were detected, and there were no differences in adverse events. A-GSH-RBCCs offer potential to reduce infectious risk in TDT with a tolerable safety profile., Ege University Hospital Blood Centre, Izmir, Turkey

Purpose: Port needle insertions are painful and distressing for Pediatric Hematology-Oncology patients. Virtual Reality (VR) can be used during needle-related procedures in these patients. This study aimed to investigate the effect of VR distraction during access to the venous port with a Huber needle in reducing needle-related pain, fear, and anxiety of children and adolescents with cancer. Methods: This randomized controlled study used a parallel trial design guided by the CONSORT checklist. The sample of children (n = 42) was allocated to the VR group (n = 21) and the control group (n = 21). Port needle related pain was assessed using the Wong-Baker Faces Pain Rating Scale after the procedure. Before and after the port needle insertion procedure, anxiety and fear assessed using self-and parent-report using the Children & rsquo;s Anxiety Meter and Child Fear Scale. The primary outcome was the patient-reported pain scores after the procedure and fear and anxiety scores before and after the procedure. Pain, anxiety, and fear scores of the two groups and within groups were analyzed and also Spearman correlation analysis was used. Results: Self-reported pain scores of patients in the VR and control group were 2.4 +/- 1.8 and 5.3 +/- 1.8, respectively. This study found a statistically significant difference between groups in pain scores (p < .001). A statistically significant difference was found between groups according to the self-and parent-reported fear and anxiety scores after the procedure. Self-reported fear scores in the VR and control group were 0.8 +/- 0.9, 2.0 +/- 1.0, self-reported anxiety scores were 2.9 +/- 2.0, 5.4 +/- 2.0, respectively (p < .001). Conclusion: Virtual reality is an effective distraction method in reducing port needle-related pain, fear, and anxiety in Pediatric Hematology-Oncology patients. ClinicalTrials.gov NCT04093154.

Introduction: Beta-thalassemia is a hereditary blood disorder with some patients requiring frequent blood transfusions. Lifelong management of the disease and its complications imposes a severe burden on patients. This study aimed to understand the indirect costs and humanistic burden, treatment preferences, and perceptions of treatment and outcomes in patients with beta-thalassemia. Methods: Systematic literature searches were conducted in Embase, MEDLINE, and MEDLINE In-Process to identify articles on patients with beta-thalassemia published between November 2010 and 2020. Studies were included if they reported on patients with beta-thalassemia of any age regarding indirect costs, health-related quality of life (HRQoL), patient/caregiver preference, and qualitative outcomes in observational, economic, and preference elicitation studies. Search methods followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane. Results: Searches yielded 2387 records; 95 publications were included (Figure). The mean annual costs due to productivity losses in patients with transfusion-dependent beta-thalassemia (TDT) was 24% of all treatment costs. The cost of lost welfare due to pain and suffering in TDT in Iran in 2015 was USD 1360.50 per year per patient. Lost opportunities for TDT patients in Iran were highest in the age group 31-40 years and lowest in the age group 0-10 years. Lost opportunities for patients' families were highest in the age group 11-20 years. The mean annual transportation cost for TDT patients in Iran for visits to hospitals was EUR 132.77 (standard deviation [SD] 15.50). The indirect burden of absenteeism due to transfusion ranged from 13.5 to 30 days in patients and 19 days in caregivers, annually. Mean indirect burden due to disease management in TDT patients was 592 min (SD 349) on transfusion days (for activities including undergoing transfusion, cross-matching of blood, arranging childcare, arranging insurance payments) and 91 min (SD 221) on non-transfusion days. No studies on indirect costs were identified in the non-transfusion dependent beta-thalassemia (NTDT) population. Blood transfusion is used to reduce pain and fatigue in TDT patients and scores for fatigue and pain were worse for a period of 5 days before transfusion (mean Brief Fatigue Inventory score 5.05 vs 4.29; mean Brief Pain Inventory-Short Forms score 4.33 vs 3.85). HRQoL outcomes were reported to be associated with age (better HRQoL in ≤14 years of age, P=0.015, P=0.008), sex (better HRQoL in males, P=0.035, P=0.041, P=0.009), lower serum ferritin (better HRQoL, P=0.05, P=0.004), compliance to iron chelation therapies (better HRQoL, P50% of TDT patients suffered from mild to severe stress, anxiety, and depression. In TDT children, mental health was the most affected domain of SF-36 compared to healthy peers (48.6 vs 96.6, P Patient preference and qualitative studies were conducted in low- and middle-income countries and findings mostly corresponded to results from HRQoL studies. Patients/caregivers frequently reported feelings of uncertainty, anxiety, depression, and thoughts of dying. Social stigma substantially affected the lives of those affected by beta-thalassemia and contributed to adverse financial impacts. Conclusions: TDT is associated with high indirect costs, including productivity losses, absenteeism, transportation cost, and societal losses. Further research is needed to understand the indirect cost burden on NTDT patients. The findings highlight the unmet need for novel therapies, and optimal disease management approaches to decrease the economic burden of TDT in patients and their caregivers. Figure 1 Figure 1. Disclosures Aydinok: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Resonance Health: Research Funding; CRISPR Therapeutics: Consultancy; SLN Therapeutics: Consultancy; Imara: Research Funding; Protagonist: Membership on an entity's Board of Directors or advisory committees, Research Funding; LaJolla: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ionis Pharmaceuticals: Research Funding. Purushotham: Evidera: Consultancy, Current Employment. Yucel: BMS: Current Employment, Current holder of individual stocks in a privately-held company. Deshpande: Evidera Ltd: Consultancy, Current Employment. Potrata: Evidera Ltd: Current Employment. Trapali: Evidera Ltd: Consultancy, Current Employment. Dixit: Evidera: Current Employment. Shah: Bristol Myers Squibb: Honoraria.

Background: Proper clinical use of blood products requires competent theoretical and practical knowledge of transfusion medicine. In this study, we aimed to evaluate levels of transfusion medicine knowledge and attainment of educational targets and identify factors affecting the education of transfusion medicine. Methods: A multicentric survey study was performed among final-year medical students. The questions were prepared based on learning objectives for transfusion medicine curriculum. The questionnaire focused on the safety of blood transfusion administration. Results: The survey included 727 (24%) of 3009 students enrolled in 13 medical schools. In the competence self-assessment, 65% of the students reported that transfusion medicine education was insufficient. Only 14% felt competent in recognizing transfusion complications and applying first-line treatment. For initiating and monitoring transfusions, 41% stated they could manage under supervision and 7% stated they had sufficient practice, while the remaining 52% considered themselves completely insufficient in this area. The 10 questions assessing basic knowledge and attainment of educational targets had 53 choices. This indicates that intern doctors were not able to recognize 50% of the correct and 30% of the incorrect information. Conclusion: A large proportion of medical students did not have adequate theoretical knowledge or self-assessed practical competency in transfusion medicine.

BACKGROUND Patients with transfusion-dependent ?-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor ? superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent ?-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P, Abbott Laboratories Novartis Alexion Pharmaceuticals Terumo BCT Celgene FibroGen: 7,988,973, 8,007,809, 8,895,016 Novartis Pharma Acceleron Vifor Pharma, Supported by Celgene in collaboration with Acceleron Pharma. Dr. Cappellini reports receiving grant support, paid to her institution, and advisory board fees from Celgene; Dr. Viprakasit, receiving consulting fees from Celgene; Dr. Taher, receiving research funding and consulting fees from Celgene; Dr. Georgiev, receiving grant support from Celgene; Dr. Kuo, receiving advisory board fees from Agios Pharmaceuticals, Apellis Pharmaceuticals, and Celgene, lecture fees and advisory board fees from Alexion Pharmaceuticals, fees for serving on a data and safety monitoring board from Bioverativ Therapeutics, consulting fees from Bluebird Bio, lecture fees and consulting fees from Novartis, and grant support and consulting fees from Pfizer; Dr. Coates, receiving advisory board fees from Agios Pharmaceuticals and Celgene and advisory board fees and consulting fees from ApoPharma; Dr. Liew, receiving grant support, paid to his institution, from Celgene; Dr. Forni, receiving advisory board fees from Bluebird Bio, Celgene, and Novartis Pharma; Dr. Lal, receiving grant support, paid to his institution, from Bluebird Bio, Insight Magnetics, La Jolla Pharmaceutical Company, Novartis, Protagonist Therapeutics, and Terumo BCT, and grant support, paid to his institution, and advisory board fees from Celgene; Dr. Kattamis, receiving advisory board fees, fees for serving on a steering committee, and travel support from Celgene, grant support, paid to his institution, and advisory board fees from Novartis, fees for serving on a trial steering committee from Vertex Pharmaceuticals, and advisory board fees from Vifor Pharma; Dr. Origa, receiving grant support from Celgene; Dr. Aydinok, receiving grant support, paid to Ege University Hospital, from Celgene; Dr. Shah, receiving advisory board fees from Bluebird Bio and Roche, advisory board fees, lecture fees, and fees for serving on a steering committee from Celgene, advisory board fees and lecture fees from Novartis, and lecture fees from Sobi; Dr. Neufeld, receiving fees for serving on a data and safety monitoring board and consulting fees from Acceleron Pharma, fees for serving on a data and safety monitoring board from ApoPharma, advisory board fees and fees for serving on a steering committee from Celgene, and advisory board fees and consulting fees from Novartis Pharma; Dr. Thompson, receiving grant support, paid to her institution, from Baxalta and BioMarin Pharmaceuticals, and grant support, paid to her institution, and consulting fees from Bluebird Bio, Celgene, and Novartis Pharma; Dr. Shetty, being employed by Celgene; Dr. Zhang, being employed by and owning stock and stock options in Celgene; Dr. Miteva, being employed by Celgene; Dr. Zinger, being employed by and owning stock options in Celgene; Dr. Linde, being employed by and owning stock in Acceleron Pharma and owning stock in Abbott Laboratories and FibroGen; Dr. Sherman, being employed by and receiving consulting fees from Acceleron Pharma and Deciphera Pharmaceuticals, receiving consulting fees from Fusion Pharma and Mersana Therapeutics and fees for serving as a board member from Newlink Genetics, Pieris Pharmaceuticals, and Pulmatrix, and holding patents 10,093,707, 8,007,809, 8,895,016, and 7,988,973 on antagonists of activin-ActRIIA and uses for increasing red-cell levels, licensed to Acceleron Pharma; Dr. Hermine, receiving grant support from Alexion Pharmaceuticals, Celgene, and Takeda California; Dr. Porter, receiving lecture fees and advisory board fees from Agios Pharmaceuticals, advisory board fees and presentation fees from Bluebird Bio, advisory board fees from Celgene, and fees for serving on a steering committee from Vifor Pharma; and Dr. Piga, receiving grant support, paid to his institution, from Acceleron and grant support, paid to his institution, and advisory fees from Celgene. No other potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. We thank the patients and families who participated in the BELIEVE trial; the investigators who collaborated in the trial; personnel at Acceleron Pharma, including Kenneth M. Attie, Xiaosha Zhang, Carolyn J. Barron, Joseph G. Reynolds, John Oram, and Tad Akers; and Daria I. Grisanzio of Excerpta Medica and Khaled Musallam and Hannah Wills of AMICULUM for writing assistance with an earlier version of the manuscript.

There are a limited number of studies evaluating iron overload in childhood leukemia by magnetic resonance imaging (MRI). The aim of this study was to determine liver iron content (LIC) by MRI in children with acute lymphoblastic leukemia (ALL) who had completed treatment and to compare those values with serum iron parameters.A total of 30 patients between the ages of 7 and 18 who had completed ALL treatment were included in the study. Serum iron parameters (serum iron, serum ferritin [SF], and total iron-binding capacity) and liver function tests were studied. R2 MRI was performed for determining LIC.Normal LIC was detected in 22 (63.4%) of the cases. Seven (23.3%) had mild and 1 (3.3%) had moderate liver iron deposition. In contrast, severe iron overload was not detected in any of the cases. LIC levels were correlated with the numbers of packed red blood cell (pRBC) transfusions (r=0.637, p0.001), pRBC transfusion volume (r=0.449, p0.013), SF levels (r=0.561, p=0.001), and transferrin saturation (r=0.353, p=0.044). In addition, a positive correlation was found between the number of pRBC transfusions and SF levels (r=0.595, p0.001).We showed that the frequency of liver iron deposition was low and clinically less significant after the end of treatment in childhood ALL patients. LIC was demonstrated to be related to SF and transfusion history. These findings support that SF and transfusion history may be used as references for monitoring iron accumulation or identifying cases for further examinations such as MRI.Çocukluk çağı lösemisinde aşırı demir yükünü manyetik rezonans görüntüleme (MRG) ile değerlendiren sınırlı sayıda çalışma vardır. Bu çalışmanın amacı, akut lenfoblastik lösemisi (ALL) olan ve tedavisini tamamlamış olan çocuklarda R2 MRI yöntemiyle karaciğer demir içeriğini (LIC) belirlemek ve serum demir parametreleriyle karşılaştırmaktır.Çalışmaya ALL tedavisini tamamlayan 7-18 yaşları arasında toplam 30 hasta alındı. Serum demir parametreleri (serum demir, serum ferritin [SF] ve toplam demir bağlama kapasitesi), karaciğer fonksiyon testleri çalışıldı. LIC’yi belirlemek için R2 MRG yöntemi kullanıldı.Olguların 22’sinde (%63,4) normal LIC saptandı. Yedi (%23,3) olguda hafif ve 1 (%3,3) olguda orta derecede karaciğerde demir birikimi mevcuttu. Buna karşılık, hiçbir olguda ciddi derecede demir birikimi tespit edilmedi. LIC seviyeleri, pRBC transfüzyonu sayısı (r=0,637, p0,001), pRBC transfüzyon miktarı (r=0,449, p0,013), SF seviyeleri (r=0,561, p=0,001) ve transferrin (r=0,353, p=0,044) ile korele saptandı. Ek olarak, pRBC transfüzyonlarının sayısı ile SF seviyeleri arasında pozitif korelasyon bulundu (r=0,595, p0,001).Çocukluk çağı ALL hastalarında tedavi bitiminden sonra karaciğer demir birikiminin sıklığının düşük ve klinik olarak daha az önemli olduğunu gösterdik. Ayrıca, LIC’nin SF ve transfüzyon öyküsü ile ilişkili olduğunu gösterdik. Bu bulgular, SF ve transfüzyon geçmişinin demir birikimini izlemek veya MRG gibi ileri tetkikin gerekli olduğu olguları belirlemek açısından referans olarak kullanılabileceğini desteklemektedir.

Effective iron chelation therapy is an important part of treatment in patients with transfusion-dependent thalassaemia and lower-risk myelodysplastic syndromes (MDS). Key strategies for optimising iron chelation therapy include ensuring good adherence and preventing and managing adverse events (AEs). Good adherence to iron chelation therapy with deferoxamine and deferasirox has been linked to improved survival and/or reductions in complications related to iron overload; however, maintaining good adherence to iron chelators can be challenging. Patients with transfusion-dependent thalassaemia or lower-risk MDS showed better adherence to the deferasirox film-coated tablet (FCT) formulation than to the deferasirox dispersible tablet formulation in the ECLIPSE trial, reflecting in part the improved palatability and convenience of deferasirox FCT. As well as affecting adherence, AEs may lead to dose reduction, interruption or discontinuation, resulting in suboptimal iron chelation therapy. Preventing and successfully managing AEs may help limit their impact on adherence, and following dosage and administration recommendations for iron chelators such as deferasirox may help minimise AEs and optimise treatment in patients with transfusion-dependent thalassaemia and lower-risk MDS.

Introduction of MRI techniques for identifying and monitoring tissue iron overload and the current understanding of iron homeostasis in transfusion-dependent (TDT) and non-transfusion-dependent thalassemia have allowed for a more robust administration of iron chelation therapies. The development of safe and efficient oral iron chelators and the insights gained from large-scale prospective studies using these agents have improved iron overload management. A significant reduction in iron toxicity-induced morbidity and mortality and improvements in quality of life were observed in TDT. The appropriate management of tissue-specific iron loading in TDT has been portrayed using evidence-based data obtained from investigational studies.

WOS: 000426572200002, PubMed ID: 28404539, Objective: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey. Materials and Methods: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with beta-thalassemia major (n = 1658, 83.4%) and intermedia (n = 215, 10.8%). Results: The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all beta-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged, Ege Children's Foundation; Novartis Pharmaceuticals CorporationNovartis, The authors thank Caglar Serdar, Aylin Gokduman, and Tolga Turgay of Plexus Information Technologies for their website support. The current study and the work presented here are from an Investigator Initiated Trial, which was sponsored by the Ege Children's Foundation and funded by Novartis Pharmaceuticals Corporation.

63rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) -- DEC 11-14, 2021 -- Atlanta, GA, [No Abstract Available], Amer Soc Hematol

Introduction: Growth retardation (GR) and pubertal disturbances are the earliest consequences of iron toxicity resulting from the pituitary iron deposition in children and adolescents with thalassemia major (TM). It is suggested that adequate transfusion regimens together with appropriate management of iron chelation with timely initiation and dose tailoring by close monitoring using surrogate markers of the iron load may achieve a normal pattern of complication-free survival in TM. Objectives: The purpose of this study was to evaluate the fact that the current approach to the management of the disease has provided a normal growth progression and sexual development in patients (pts) with TM. Methods: We recruited male (M) and female (F) TM pts born after 2000 and followed-up (FU) in Ege University Thalassemia Center. The pts. with an acute or chronic illness that may interfere with growth and development or stem cell transplantation recipients were excluded. The Committee of Clinical Investigation at Ege University Hospital (19.02.2020, 20-2.1T/2) approved this study. Height (H) and weight (W) assessments were performed by using the Harpenden stadiometer and puberty was evaluated by Tanner staging at 3 monthly intervals. H-standard deviation scores (h-SDS) were calculated. Target-H based on mid-parental-H for M & F pts was estimated. All pts. were evaluated annually for bone mineral density (BMD) using dual-energy X-ray absorptiometry (Hologic QDR-4500W, USA) after 8 years (y) of age. The mean SDS of the lumbar spine (L1-4) BMD between -1 and -2.5 was defined as osteopenia and Transfused pRBC units (U) and average pre-transfusion hemoglobin (Hb) per year were recorded. Serum ferritin (SF) was monitored at monthly intervals. Myocardial (T2*) and liver (R2) iron were assessed by a 1.5 Tesla magnetic resonance imaging (MRI) machine (Siemens, Symphony Vision 16034 scanner) after 8 y. Annual median SF, prescribed chelator(s), mean chelator doses were recorded by reviewing pts' records. Transfusional iron intake (TII) was estimated as the total amount of pure RBCs (each U, 250 ml with 57% Hct) transfused in a y (ml) x 1.08. Daily TII was expressed as annual TII (mg)/ mean kg b.w./days of the y. Results: We recruited 30 TM (28 β/β, 1 β/δβ, and 1 non-deletional HbH) pts (13 F and 17 M). Demographics for the population are summarized in Table1. All pts maintained annual mean pre-transfusion Hb> 9 g/dl. Twenty-two of 24 pts maintained Deferasirox (DFX) chelation during 9 ± 3.6 y (median 9, range 2-13 y) and achieved optimum SF levels at all times (Figure a). The dose tailoring of DFX found parallel to the changes in TII during FU (Figure b). Liver iron concentration (LIC) and myocardial T2* (mT2*) in 22 pts on DFX chelation were between 0.9-5.4 (2.1 ± 1.3 SD) mg Fe/g d.w. and 19.4-43.5 (28 ± 6.7 SD) ms, respectively, in all assessments. The only pt with mT2* of 19.4 ms revealed mT2* of >20 ms on FU scans. The puberty initiated at 12.8 ± 1.1 y in M (n=12) & 11.2 ± 1.3 y in F (n=12) and progressed without hormone replacement in all, regardless of the chelator. Overall, growth reduced compared to the non-thalassemic population after 8 y with clear evidence of growth catch-up by the introduction of puberty. h-SDS detected Conclusions: Puberty was the main determinant of growth and bone maturation in TM. Despite, puberty has achieved within physiological limits in M & F pts, a slight delay was observed compared to the non-thalassemic population. The relative delay in pubertal spurt may lead to overdiagnosis of growth and bone-maturation failure and unnecessary intervention in adolescent TM pts. This hypothesis as well as the appropriateness of current management guidelines remains to be elucidated. Disclosures No relevant conflicts of interest to declare.

Purpose To compare the effects of the care bundles including chlorhexidine dressing and advanced dressings on the catheter-related bloodstream infection (CRBSI) rates in pediatric hematology-oncology patients with central venous catheters (CVCs). Method Twenty-seven PHO patients were recruited to participate in a prospective, randomized study in Turkey. The researcher used care bundles with chlorhexidine dressing in the experimental group (n = 14), and care bundles with advanced dressings in the control group (n = 13). Results According to the study results, 28.6% of the patients in the experimental group had CRBSI, while this rate was 38.5% in the control group patients. The CRBSI rate in the experimental group was 3.9, and the control group had 4.4 per 1000 inpatient catheter days. There was no exit-site infection in the experimental group. However, the control group had 1.7 per 1000 inpatient catheter days. Conclusions Even though there was no difference between the two groups in which the researcher implemented care bundles with chlorhexidine dressing and advanced dressings in terms of CRBSI development, there was reduction in the CRBSI rates thanks to the care bundle approach. It is possible to control the CRBSI rates using care bundles in pediatric hematology-oncology patients.

WOS: 000396425800003, PubMed ID: 27815226, Objectives: Invasive aspergillosis (IA) is an important cause of mortality and morbidity in children with hematological malignancies. The monitoring of serum galactomannan (GM) antigen is considered useful in the diagnosis of IA. The aim of this study was to determine the utility of serum GM monitoring in the early diagnosis of IA and the role of positive antigenemia in the management of children with acute lymphoblastic leukemia (ALL). Methods: The cases of 141 children who were being treated for ALL in the Division of Pediatric Hematology of the Medical School of Ege University between January 2006 and February 2015 were reviewed retrospectively. Cases of proven and probable IA were defined according to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. Results: The incidence of proven and probable IA was 3.5% (5/141). The incidence of positive GM antigenemia among 3264 serum samples was 5.5% (n = 179). Of the cases detected, 21.7% were truepositive, 52.1% were false-positive, and the remaining 26.1% were classified as 'undetermined.' An increase in the incidence of true-positive tests and induction of antifungal therapy was determined through multiple consecutive positive tests. Conclusions: GM may be detected in the serum before the clinical signs of IA appear, but its sensitivity and specificity are variable. False-positivity is a significant disadvantage, and consecutive positive GM must be taken into account in the case of clinical and imaging findings that are relevant to IA. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

In beta-thalassemia, the mechanism driving ineffective erythropoiesis (IE) is insufficiently understood. We analyzed mice affected by beta-thalassemia and observed, unexpectedly, a relatively small increase in apoptosis of their erythroid cells compared with healthy mice. Therefore, we sought to determine whether IE could also be characterized by limited erythroid cell differentiation. In thalassemic mice, we observed that a greater than normal percentage of erythroid cells was in S-phase, exhibiting an erythroblast-like morphology. Thalassemic cells were associated with expression of cell cycle-promoting genes such as EpoR, Jak2, Cyclin-A, Cdk2, and Ki-67 and the antiapoptotic protein Bcl-X(L). The cells also differentiated less than normal erythroid ones in vitro. To investigate whether Jak2 could be responsible for the limited cell differentiation, we administered a Jak2 inhibitor, TG101209, to healthy and thalassemic mice. Exposure to TG101209 dramatically decreased the spleen size but also affected anemia. Although our data do not exclude a role for apoptosis in IE, we propose that expansion of the erythroid pool followed by limited cell differentiation exacerbates IE in thalassemia. In addition, these results suggest that use of Jak2 inhibitors has the potential to profoundly change the management of this disorder.

Objective: In recent years, the rates of marriage and pregnancy are increasing in patients with thalassemia major. The aim of the present study was to investigate the fertility rate of thalassemic patients and the course of pregnancies in terms of mother and infant health. Materials and Methods: In this observational study patients with major hemoglobinopathy were evaluated regarding marital status, the need for assisted reproductive techniques, fertility rate, iron status, and pregnancy complications. Results: Seventeen female patients gave birth to 21 healthy infants. About one-third of the patients needed assisted reproductive techniques. Thalassemia major patients showed increased serum ferritin levels from 1203±1206 µg/L at baseline to 1880±1174 µg/L at the end of pregnancy. All babies are still alive and healthy. Conclusion: Pregnancy in patients with thalassemia can be safe for the mother and newborn with close monitoring and a multidisciplinary approach., Amaç: Son yıllarda, talasemi majör olgularının evlilik ve gebelik oranları giderek artmaktadır. Bu çalışmanın amacı, talasemi hastalarının fertilite oranlarının araştırılması ve anne ve bebek sağlığı açısından gebelik sonuçlarının değerlendirilmesidir. Gereç ve Yöntemler: Bu gözlemsel çalışmada; majör hemoglobinopatili hastalar; evlenme ve çocuk sahibi olma oranları, yardımcı üreme tekniklerine gereksinimleri, demir statüleri ve gebelik komplikasyonları açısından değerlendirilmiştir. Bulgular: On yedi talasemik kadın hasta, toplam 21 sağlıklı bebek doğurmuştur. Hastaların üçte biri bebek sahibi olabilmek için yardımcı üreme tekniğine ihtiyaç duymuştur. Talasemi majör olgularının serum ferritin değerleri hamileliğin başında ortalama 1203±1206 ug/L saptanmış olup, hamileliğin sonunda 1880±1174 ug/L seviyesine yükselmiştir. Tüm bebekler halen hayatta ve sağlıklıdırlar. Sonuç: Talasemi olgularında hamilelik süreci yakın takip ve multidisipliner yaklaşım ile beraber güvenli olarak geçirilebilecektir.

EgeUn###, Central line–associated bloodstream infections (CLABSIs) are still a major cause of morbidity and mortality in pediatric hematology-oncology patients in many countries. This cross-sectional study was a retrospective review of CLABSI in inpatient pediatric hematology-oncology cases with long-term central venous catheter at the Pediatric Hematology Department from January 2013 to June 2014. Characteristics of CLABSI events in pediatric patients with hematologic malignancies and related nonmalignant hematologic conditions are documented. CLABSI developed in 61.8% (n = 21) of the 34 hospitalized patients included in the study. The CLABSI rate was 7.8 per 1,000 inpatient central venous catheter days. Coagulase-negative staphylococci was the predominant pathogen in 47.6% of the patients with CLABSI. The high rate of CLABSI requires prevention strategies to reduce CLABSI immediately. This study provides guidance in prioritizing strategies for reducing rates of infection. © 2019 by Association of Pediatric Hematology/Oncology Nurses.

Amac : Bu calismada akut lenfoblastik losemi (ALL) on tanili olgularda t(12;21) translokasyonu gercek zamanli kantitatif revers transkriptaz polimeraz zincir reaksiyonu (qRT-PZR) yontemi kullanilarak kantite edildi. Hastalar ve yontemler : Ocak 2009 - Aralik 2013 tarihleri arasinda Ege Universitesi Tip Fakultesi Tibbi Biyoloji Anabilim Dali’na basvuran 175 pediatrik ve 138 eriskin olmak uzere toplam 313 olguya ait kan ve kemik iligi orneklerinde t(12;22) (p13;q22) translokasyonu RNA sonuclari kantitatif olarak degerlendirildi. Olgulara ait 75 kan ve 484 kemik iligi orneklerinden total RNA veya haberci RNA izole edildi. RNA izolasyonlarinin ardindan tamamlayici DNA sentezi gerceklestirildi. t(12;21) (p13;q22) translokasyon calismasi LightCycler t(12;21) Kit’i ile fuzyon transkripte ozgul bicimde tasarlanmis primer ve problarla (Way2Gene) uygun olacak sekilde gerceklestirildi. Son adim olarak, t(12;21) translokasyon sonuclarinin kantitatif olarak degerlendirilmesi gercek zamanli qRT-PZR yontemi kullanilarak LightCycler2 ile gerceklestirildi. Bulgular : Otuz dort pediatrik olgu orneginde (%19) ve 17 eriskin olgunun orneginde (%12) TEL-AML-1 (ETV6-RUNX1) pozitif bulundu. TEL-AML1 (ETV6-RUNX1) kantitasyon degeri ortalamasi pediatrik olgularda 0.90±3.21, eriskin olgularda ise 0.34±1.20 olarak belirlendi. Sonuc : Elde ettigimiz veriler, gercek zamanli qRT-PZR yontemi ile ALL hastalarinda yeni tani doneminde ve tedavi surecinde t(12;21) translokasyonunun kantitatif tayininin hem taninin kesinlestirilmesinde hem de molekuler remisyon saglanmasina yonelik tedaviyi yonlendirmesinde degerli bir yontem oldugunu desteklemektedir.

WOS: 000370467700004, PubMed ID: 26852651, Efficacy and safety of iron chelation therapy with deferasirox in iron-overloaded non-transfusion-dependent thalassaemia (NTDT) patients were established in the THALASSA study. THETIS, an open-label, single-arm, multicentre, Phase IV study, added to this evidence by investigating earlier dose escalation by baseline liver iron concentration (LIC) (week 4: escalation according to baseline LIC; week 24: adjustment according to LIC response, maximum 30 mg/kg/day). The primary efficacy endpoint was absolute change in LIC from baseline to week 52. 134 iron-overloaded non-transfusion-dependent anaemia patients were enrolled and received deferasirox starting at 10 mg/kg/day. Mean actual dose +/- SD over 1 year was 14.70 +/- 5.48 mg/kg/day. At week 52, mean LIC SD decreased significantly from 15.13 +/- 10.72 mg Fe/g dw at baseline to 8.46 +/- 6.25 mg Fe/g dw (absolute change from baseline, -6.68 +/- 7.02 mg Fe/g dw [95% CI: -7.91, -5.45]; P, Novartis Pharma AG; Novartis Pharmaceuticals, This study was funded by Novartis Pharma AG. We thank Rebecca Helson, PhD, of Mudskipper Business Ltd. for medical editorial assistance. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals.

Introduction. LPS-responsive beige-like anchor (LRBA) protein deficiency is a disease of immune dysregulation with autoimmunity affecting various systems. Case Presentation. Two male siblings with a novel LRBA mutation had different primary findings at admission: the younger sibling had chronic early-onset diarrhoea and the elder one had autoimmune haemolytic anaemia. During long-term follow-up for IPEX phenotype, both developed hypogammaglobulinaemia, enteropathy and lung involvement. The patients partially responded to immunosuppressive therapies. A homozygous c.2496C>A, p.Cys832Ter (p.C832*) mutation in the LRBA gene causing a premature stop codon was detected. After molecular diagnosis, abatacept, as a target-specific molecule, was used with promising results. Conclusion. LRBA deficiency is a recently defined defect, with variable presentations in different patients; a single, definitive treatment option is thus not yet available.

WOS: 000434010200026, PubMed ID: 29756724, Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare mucocutaneous diseases which are associated with a prolonged course and potentially lethal outcome. They are mostly drug induced and mortality rates are very high. Although mostly skin is involved, multiple organ systems such as cardiovascular, pulmonary, gastrointestinal, and urinary systems may be affected. Here, we report a case of Stevens-Johnson Syndrome associated with methotrexate treatment who developed acute cardiac failure and gastrointestinal hemorrhage beside skin findings. He had been treated with intravenous immunglobulin and methylprednisolone succesfully and continued chemotherapy with methotrexate treatment again.

Experiences with new multikinase inhibitors are limited, especially in children. In this report we summarize our experience with 2 patients with relapsed acute myeloblastic leukemia (AML), one with FMS-like tyrosine kinase-3-internal tandem duplication mutation and the other with a single base mutation (D835Y). Both patients received sorafenib, one for 19 days and the other for 42 days, with clofarabine-including chemotherapy. One additionally received sunitinib for a total of 20 days. Both patients developed severe pancytopenia, hypertension, life-threatening bleedings from the gastrointestinal system, and, finally, intrapulmonary hemorrhage. Although both reached severe aplasia of the bone marrow without blastic infiltration, death occurred with neutropenic sepsis.Multikinaz inhibitörleri ile deneyim, özellikle çocuklarda çok sınırlıdır. Burada, biri FMS-like tirozin kinaz 3-ITD ve diğeri tek baz mutasyonu (D835Y) taşıyan nüks akut miyeloblastik lösemi (AML) tanılı iki hastadan edindiğimiz deneyimi sunmak istedik. Her iki hasta sorafenib (biri 19, diğeri 42 gün olmak üzere) tedavisini klofarabin içeren yoğun kemoterapi protokolü ile birlikte aldı. D835Y mutasyonu bulunan hasta daha sonra 20 gün sunitinib ile tedaviye devam etti. Her iki hastada da ağır pansitopeni, hipertansiyon, yaşamı tehdit eden gastrointestinal sistem kanaması ve pulmoner kanama gelişti. Her iki hastanın kemik iliğinde ağır bir aplazi sağlanmış olsa da blastik infiltrasyon görülmeden nötropenik sepsisle hastalar kaybedildi.

Amaç: t(4;11), MLL-AF4 translokasyonu sonucu oluşan, 4q21 kromozomal bandına yerleşim gösteren AF4 geninin 11q23 kromozomal bandına yerleşim gösteren MLL genine füzyonu sonucu gelişen kromozomal bir anomalidir. Bu çalışmada, retrospektif olarak 2009-2013 yılları arasındaki akut lenfoblastik lösemi (ALL) hastalarındaki t(4;11) MLL- AF4 translokasyonunun analiz sonuçlarının incelenmesi amaçlandı. Gereç ve Yöntem: Ege Üniversitesi Tıp Fakültesi Tıbbi Biyoloji Anabilim Dalı’na 2009-2013 yılları arasında akut lösemi ön tanısıyla 176 çocuk (70 kız, 106 erkek) ve 144 yetişkin (60 kadın, 84 erkek) olgunun kan veya kemik iliği örnekleri incelendi. Bu olgulara ait 71 kan ve 473 kemik iliği örneğinin t(4;11) translokasyon RNA sonuçları, gerçek zamanlı RT-PCR yöntemi ile kantitatif olarak değerlendirildi. İlk aşamada, kan ve kemik iliği örneklerinden izole edilen total RNA veya mRNA’dan konvansiyonel bir PCR cihazı ile komplementer DNA sentezlendi. İkinci aşamada, gerçek zamanlı PCR cihazı ile t(4;11) kantitasyonu gerçekleştirildi. Olguların kantitatif olarak değerlendirilmesi, pozitif kontrol ve negatif kontrolün karşılaştırılması ile örneklerin negatif yada pozitif (pozitif olgu kopya sayısının referans kopya sayısına oranı) olması şeklinde yapıldı. Bulgular: Çalışmamızda 98’i takip hastası olmak üzere toplam 320 hasta t(4;11) MLL-AF4 translokasyonu için değerlendirildi. Çalışmaların sonucunda toplam 34 olgu (24 çocuk, 10 yetişkin) pozitif ve diğer örnekler negatif olarak bulundu. Sonuç: Bu değerlendirmenin sonuçları, RT-PCR yöntemi ile ALL hastalarında yeni tanı döneminde ve tedavi sürecinde t(4;11) MLL-AF4 translokasyonunun kantitatif tayini, hem tanının kesinleştirilmesinde hem de moleküler remisyon sağlanmasına yönelik tedaviyi yönlendirmesinde değerli bir yöntem olduğunu desteklemektedir., Aim: t(4,11) is a chromosomal abnormality formed by the translocation MLL-AF4, which is the result of the fusion of the AF4 gene, localized on 4q21 chromosomal band, to the MLL gene, localized on 11q23 chromosomal band. The aim of this study is to examine the results of the analysis of t (4;11) MLL-AF4 translocation in acute lymphoblastic leukemia (ALL) patients retrospectively. Materials and Methods: Peripheral blood or bone marrow samples of 176 children (70 girls, 106 boys) and 144 adults (60 women, 84 men) with a preliminary diagnosis of acute leukemia between 2009-2013 were analyzed in the Medical Biology Department of Ege University Faculty of Medicine. The translocation RNA results of 71 peripheral blood and 473 bone marrow samples of these patients were evaluated quantitatively for t(4;11) with real-time RT- PCR. t(4;11) quantitation was performed by real-time qRT-PCR instrument after the synthesis of complementary DNA with conventional PCR from total RNA or mRNA isolated from blood and bone marrow. Quantitative analysis of the patients was performed by comparing positive and negative controls and samples classified as positive or negative (the ratio of the number of positive copies to the number of reference copies). Results: A total of 320 patients, with 98 having also follow-ups, were evaluated for t(4;11) translocation. Totally 34 patients (24 children and 10 adults) were found positive and the other samples were negative. Conclusion: The assessment of these results supports that, quantitative determination of t(4;11) with RT-PCR method among newly diagnosed ALL patients and ALL patients undergoing treatment, is a valuable method for both confirming the diagnosis and guiding the treatment intended to achieve molecular remission.

Amac: Bu calismada, Ege Universitesi Tip Fakultesi Tibbi Biyoloji Anabilim Dali'na 2009-2013 yillari arasinda akut myeloid losemi (AML) on tanisi ile basvuran 402 olgunun (322 yetiskin, 80 cocuk) kan veya kemik iligi orneklerinin inv16 kantitasyon analizlerinin RT-PCR yontemi ile degerlendirilmesi amaclandi. Gerec ve Yontem: Hastalardan alinan kan ve kemik iligi orneklerinden total RNA/mRNA izolasyonunu takiben cDNA'lari elde edilerek revers-transkriptaz-polimeraz zincir reaksiyonu (RT-PCR) yontemiyle inv16 kantitasyonu LightCycler2 cihazinda gerceklestirildi. Bulgular: Dort yuz iki olgu, inv(16) CBFBETA-MYH11 inversiyonu acisindan degerlendirildi. Yapilan analiz sonucunda 12 (% 4) eriskin ve 7 (% 9) cocuk olmak uzere toplam 19 olguda inv16 pozitifligi saptandi. Sonuc: Inv16 kantitatif analizi, AML hastalarinin klinik degerlendirilmesinde, hastaligin seyri ve remisyon saglanmasina yonelik tedavi protokollerinin uygulanmasinda etkili bir yontem oldugunu desteklemektedir. AML hasta grubunu iceren daha genis kapsamli calismalar yapilarak elde edilen sonuclar desteklenmelidir.

Despite improvements in diagnosis and treatment, invasive fungal infections (IFIs) are still a major cause of morbidity and mortality in immunocompromised patients. The data on IFI among children with acute lymphoblastic leukaemia (ALL) are still scarce, and our aim was to estimate the risk, aetiology and outcome of proven and probable IFIs in children with ALL who did not receive primary prophylaxis over an 8-year period. Between January 2005 and February 2013, 125 children who were treated for ALL at the Pediatric Hematology Department of the Medical School of Ege University were retrospectively reviewed. Proven and probable IFIs were defined according to revised definitions of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. The proven and probable IFI incidence was 30/125 (24%). Profound neutropenia was detected in 18 (60%) patients, and prolonged neutropenia was detected in 16 (53.3%) of the patients. The most isolated agents were non-albicans Candida spp. The crude and attributable mortality was 20% and 13.3% respectively. Profound neutropenia was associated with mortality (P < 0.05). The younger patients were especially at risk for proven IFI. Prolonged neutropenia, to be in the induction phase of chemotherapy, and profound neutropenia were found to be the most common predisposing factors for IFI episodes.

PubMedID: 25345697 Long-term controlled studies are needed to inform on the clinical benefit of chelation therapy for myocardial iron removal in transfusion-dependent beta thalassemia patients. In a 1-year nonrandomized extension to the CORDELIA study, data collected from patients with myocardial siderosis provided additional information on deferasirox or deferoxamine (DFO) efficacy and safety. Myocardial (m)T2* increased from baseline 11.6 to 15.9 ms in patients receiving deferasirox for 24 months (n = 74; geometric mean [Gmean] ratio of month 24/baseline 1.38 [95% confidence interval 1.28, 1.49]) and from 10.8 to 14.2 ms in those receiving DFO (n = 29; Gmean ratio 1.33 [1.13, 1.55]; P = 0.93 between groups). Improved mT2* * with deferasirox was evident across all subgroups evaluated irrespective of baseline myocardial (mT2* < 10 vs. ? 10 ms) or liver (LIC

PubMed ID: 28940308, Our phase I, open-label, multi-center, dose-escalation study evaluated the pharmacokinetics (PK) of SP-420, a tridentate oral iron chelating agent of the desferrithiocin class, in patients with transfusion dependent ß-thalassemia. SP-420 was administered as a single dose of 1.5 (n = 3), 3 (n = 3), 6 (n = 3), 12 (n = 3), and 24 (n = 6) mg/kg or as a twice-daily dose of 9 mg/kg (n = 6) over 14-28 days. There was a near dose-linear increase in the mean plasma SP-420 concentrations and in the mean values for C max and AUC 0-? over the dose range evaluated. The median t max ranged from 0.5 to 2.25 h and was not dose dependent. The study was prematurely terminated by the sponsor due to renal adverse events (AE) including proteinuria, increase in serum creatinine, and one case of Fanconi syndrome. Other adverse effects included hypersensitivity reactions and gastrointestinal disturbances. Based on current dose administration, the renal AE observed outweighed the possible benefits from chelation therapy. However, additional studies assessing efficacy and safety of lower doses or less frequent dosing of SP-420 over longer durations with close monitoring would be necessary to better explain the findings of our study and characterize the safety of the study drug. © 2017 Wiley Periodicals, Inc., This was a phase Ib, dose-escalation study assessing SP-420 in b-thalassemia patients with chronic transfusional iron overload requiring treatment with an iron chelator. Patients were enrolled from study centers in Canada, Lebanon, Thailand, and the United States from December 2014 through August 2015. This study was funded by Sideris Pharmaceuticals.

WOS: 000394910900011, PubMed ID: 27859648, BackgroundIn transfusion-dependent anaemias, while absolute serum ferritin levels broadly correlate with liver iron concentration (LIC), relationships between trends in these variables are unclear. These relationships are important because serum ferritin changes are often used to adjust or switch chelation regimens when liver magnetic resonance imaging (MRI) is unavailable. Objectives and methodsThis post hoc analysis of the EPIC study compared serum ferritin and LIC in 317 patients with transfusion-dependent thalassaemia before and after 1 yr of deferasirox. ResultsSerum ferritin responses (decreases) occurred in 73% of patients, 80% of whom also have decreased LIC. However, 52% of patients without a serum ferritin response did decrease LIC and by >1 mg Fe/g dw (median 3.9) in 77% of cases. Absolute serum ferritin and LIC values correlated significantly only when serum ferritin was, Novartis Pharma AG; Novartis Pharmaceuticals, This study was sponsored by Novartis Pharma AG. Medical writing support was provided by Debbi Gorman and Catherine Risebro, PhD, from Mudskipper Business Ltd, funded by Novartis Pharmaceuticals.

Introduction: β-thalassemia is an inherited hemoglobinopathy associated with an erythroid maturation defect characterized by ineffective erythropoiesis and impaired RBC maturation. Luspatercept is a first-in-class erythroid maturation agent under development to treat patients with β-thalassemia. Luspatercept binds to select TGFβ superfamily ligands to reduce aberrant Smad2/3 signaling and enhance late-stage erythropoiesis (Suragani RN, et al. Nat Med. 2014;20:408-14). We report the results of a phase 3, randomized, double-blind, placebo-controlled study to determine the efficacy and safety of luspatercept in adult β-thalassemia patients requiring regular RBC transfusions. ClinicalTrials.gov identifier: NCT02604433. Methods: Eligible patients were aged ≥ 18 years; had β-thalassemia or hemoglobin (Hb) E/β-thalassemia (compound β-thalassemia mutation and/or multiplication of α-globin genes was allowed); and required regular transfusions of 6-20 RBC units in the 24 weeks prior to randomization with no transfusion-free period ≥ 35 days during that time. Patients were randomized 2:1 to receive either luspatercept, at a starting dose level of 1.0 mg/kg with titration up to 1.25 mg/kg, or placebo, subcutaneously every 3 weeks for ≥ 48 weeks. Patients in both treatment arms continued to receive RBC transfusions and iron chelation therapy to maintain the same baseline Hb level. The primary endpoint was a ≥ 33% reduction in transfusion burden (with a reduction of ≥ 2 RBC units) during weeks 13-24, when compared with a 12-week baseline period. Key secondary endpoints included: ≥ 33% reduction in RBC transfusion burden at weeks 37-48, ≥ 50% reduction in transfusion burden at weeks 13-24, ≥ 50% reduction in transfusion burden at weeks 37-48, and mean change in transfusion burden at weeks 13-24. Achievement of ≥ 33% reduction in RBC transfusion burden over any consecutive 12 weeks on study was also evaluated. Results: † A total of 336 patients were randomized, of whom 332 were treated. Median age was 30 years (range 18-66) and 58% of patients were female. Patients received a median of 6 RBC units in the 12 weeks prior to treatment. 58% of patients in each arm had undergone splenectomy. B0/B0 genotype (classification according to the HbVar database) was observed in 68 of 224 (30.4%) and 35 of 112 (31.3%) patients in the luspatercept and placebo arms, respectively. 48 of 224 (21.4%) patients in the luspatercept arm achieved the primary endpoint versus 5 of 112 (4.5%) patients receiving placebo (odds ratio 5.79, P < 0.0001). 44 of 224 (19.6%) patients receiving luspatercept achieved a ≥ 33% reduction in RBC transfusion burden at weeks 37-48 compared with 4 of 112 (3.6%) patients receiving placebo (P < 0.0001). Of 224 patients receiving luspatercept, 17 (7.6%) and 23 (10.3%) achieved a ≥ 50% reduction in RBC transfusion burden at weeks 13-24 and 37-48, respectively, compared with 2 (1.8%) and 1 of 112 (0.9%) patients receiving placebo (P = 0.0303 and P = 0.0017, respectively). The difference of mean change from baseline in transfusion burden from week 13 to week 24 was 1.35 units (P < 0.0001). 158 of 224 (70.5%) patients receiving luspatercept achieved a ≥ 33% RBC transfusion reduction over any consecutive 12 weeks compared with 33 of 112 (29.5%) patients receiving placebo (P < 0.0001); statistically significant differences were also noted for all other transfusion burden reduction endpoints. Adverse events (AEs) observed in the study were generally consistent with previously reported phase 2 data. Treatment-emergent AEs leading to dose delay or dose reduction were similar between treatment arms. No patient deaths were reported for those treated with luspatercept. Conclusions: Treatment with luspatercept resulted in significant reductions in RBC transfusion burden in adults with transfusion-dependent β-thalassemia. Luspatercept was generally well tolerated in this patient population. † As of May 11, 2018, cutoff date. Disclosures Cappellini: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Sanofi/Genzyme: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Vifor: Membership on an entity's Board of Directors or advisory committees. Viprakasit:F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Protagonist Therapeutics: Consultancy, Research Funding. Taher:Protagonist Therapeutics: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; Ionis Pharmaceuticals: Consultancy; La Jolla Pharmaceutical: Research Funding; Celgene Corp.: Research Funding. Georgiev:Alnylam: Consultancy. Coates:Celgene Corp.: Consultancy; ApoPharma: Consultancy, Honoraria; Vifor Pharma: Consultancy; Sangamo: Consultancy, Honoraria. Voskaridou:Acceleron: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding. Forni:Novartis: Research Funding; Roche: Research Funding; Celgene: Research Funding. Perrotta:Acceleron Pharma: Research Funding; Novartis: Research Funding. Lal:Celgene Corporation: Research Funding; Bluebird Bio: Research Funding; La Jolla Pharmaceutical Company: Consultancy, Research Funding; Insight Magnetics: Research Funding; Novartis: Research Funding; Terumo Corporation: Research Funding. Kattamis:ApoPharma: Honoraria; Vifor Pharma: Consultancy; CELGENE: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Vlachaki:Novartis: Honoraria. Origa:Cerus Corporation: Research Funding; Bluebird Bio: Consultancy; Novartis: Honoraria; Apopharma: Honoraria. Aydinok:TERUMO: Research Funding; Protagonist: Other: SSC; CRISPR Tech: Other: DMC; Cerus: Honoraria, Research Funding; La Jolla Pharmaceuticals: Research Funding; Novartis: Research Funding, Speakers Bureau; Celgene: Research Funding. Ho:Takeda: Honoraria, Other: travel to meeting; Novartis: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Celgene: Other: Travel to meeting. Chew:Celgene: Research Funding. Tantiworawit:Celgene: Honoraria, Research Funding, Speakers Bureau. Shah:Novartis: Honoraria, Speakers Bureau; Sobi/Apotex: Honoraria; Celgene Corp: Other: Steering committee; Roche: Other: Advisory board meeting. Neufeld:Celgene Corp.: Consultancy, Other: Steering committee; Acceleron Pharma: Consultancy. Laadem:Celgene: Employment, Equity Ownership. Shetty:Celgene: Employment, Equity Ownership. Zou:Celgene Corporation: Employment, Equity Ownership. Miteva:Celgene Corporation: Employment, Other: grants. Zinger:Celgene Corporation: Employment. Linde:AbbVie: Equity Ownership; Abbott Laboratories: Equity Ownership; Fibrogen: Equity Ownership; Acceleron Pharma: Employment, Equity Ownership. Sherman:Acceleron Pharma: Employment, Equity Ownership. Hermine:AB Science: Consultancy, Equity Ownership, Honoraria, Research Funding; Celgene Corporation: Research Funding; Hybrigenics: Research Funding; Erythec: Research Funding; Novartis: Research Funding. Porter:Cerus: Honoraria; Agios: Honoraria; Novartis: Consultancy. Piga:La Jolla: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Honoraria; Apopharma: Honoraria, Research Funding; Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Acceleron: Research Funding.

Introduction: Transfusion dependent thalassemia (TDT) requires regular transfusion of red cell concentrates (RBCC) to prevent the complications of anemia and excessive erythroid expansion. Despite donor testing, long-term transfusion has a substantial cumulative risk of transfusion-transmitted infection (TTI) due to undetected viruses, bacteria, and protozoa. Splenectomized (-S) TDT patients may have greater TTI morbidity than patients with spleens (+S); but may benefit from reduced use of red blood cell concentrates (RBCC) and reduced transfusion iron (Fe) loading. Pathogen reduction (PR) of RBCC with amustaline-glutathione (A-GSH) offers potential to reduce the risk of TTI. Objectives: To determine, the impact of PR-RBCC on hemoglobin (Hb) use, transfused Fe burden, incidence of RBC antibodies, and safety in -S and +S TDT patients. Methods: TDT patients at 3 sites, not stratified by spleen status, were prospectively enrolled in a two- period cross-over study randomized by sequence for RBCC preparation. Leukocyte reduced PR-RBCC (Test) were treated with 0.2mM amustaline and 20 mM GSH, re-suspended in saline-adenine-glucose mannitol (SAGM), and stored up to 35 days at 4°C. Leukocyte reduced conventional RBCC (Control) were suspended in SAGM and stored for up to 35 days at 4°C. Patients received 6 transfusions in each treatment sequence of Test or Control RBCC over ~ 5 months. Clinicians, blinded to RBCC Hb content and treatment sequence, ordered RBCC to maintain targeted pre-transfusion Hb thresholds of ~ 9-10 g/dL. Transfusion intervals or number of RBCC transfused were adjusted for clinical management. The primary efficacy outcome was assessed by non-inferiority (NI) analysis for Hb use (expressed as g/kg body weight/ day) using a pre-specified NI margin (≤ 15% of the observed Control mean). Results : Overall, mean (SD) Hb content (g) of 1024 Test RBCC = 54.6±5.9 (range: 39-73) and of 1008 Control RBCC = 55.6 ± 5.9 (range: 35-74) and varied widely. By intent-to-treat (ITT), 80 patients (40 +S and 40 -S) were transfused. For ITT patients (Table), the baseline Hb level (BL-Hb, g/dL) at first transfusion of Control periods was significantly lower than at Test periods; but the mean number of RBCC transfused, RBCC storage days, total Hb dose (g), and transfusion intervals were not significantly different for Test and Control. ITT analysis for all transfusion episodes showed Hb use for Test RBCC (0.110 g/kg/d) was not different from Control RBCC (0.112 g/kg/day). Non-inferiority was demonstrated (T-C = - 0.002 g/kg/d: 95% CI: -0.005, 0.001). ITT Test patients received a slightly lower mean total Hb dose (- 14g), and mean pre-transfusion Hb levels declined after 6 transfusions (9.4 to 8.8 g/dL). -S patients had lower BL-Hb levels (g/dL) than S+ patients in Test (9.2 vs 9.7) and Control (8.8 vs 9.2) periods (Table). -S patients received a lower mean total Hb dose of Test than Control RBCC (p=0.019); and had a decline in mean pre-transfusion Hb levels during Test periods (from 9.2 to 8.7 g/dL). Transfusion intervals were significantly longer for -S patients than +S patients with both Test and Control RBCC (p< 0.001 by 2-sample t test, respectively); and -S patients had lower Hb use than +S patients. However, Hb use of Test and Control RBCC was comparable within -S and + S cohorts (Table). Transfused Fe was less for -S patients for Test and Control RBCC. During 6 Test and 3 Control treatment periods, 8 patients (6 -S, 2 +S) had worsening anemia with pre-transfusion Hb levels (6.0-7.8 g/dL) substantially below the targeted transfusion threshold, but without evidence of hemolysis. Each of these patients received one or more Hb doses below the average RBCC transfusion episode dose (Test: 114.5 g) or (Control: 116.7 g); and 3 patients had concurrent infections. None of 80 patients had evidence of increased RBC clearance, developed antibodies to PR-RBCC, or had treatment emergent RBC alloantibodies in either treatment period. There were no differences in the overall safety profiles for Test and Control RBCC. Conclusions: Amustaline-GSH PR treatment of RBCCs offers the potential to reduce TTI risk without impacting Hb use or Fe burden in TDT. However, Hb content of Test and Control RBCC varies widely and may contribute to unexpected changes in pre-transfusion Hb levels. Spleen status affected Hb use comparably for PR-RBCC and Control RBCC, and remains an important factor in assessing transfusion requirements and Fe loading. Table. Table. Disclosures Aydinok: TERUMO: Research Funding; Cerus: Honoraria, Research Funding; CRISPR Tech: Other: DMC; Protagonist: Other: SSC; La Jolla Pharmaceuticals: Research Funding; Celgene: Research Funding; Novartis: Research Funding, Speakers Bureau. Piga:Apopharma: Honoraria, Research Funding; Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding; La Jolla: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Honoraria; Acceleron: Research Funding; Novartis: Research Funding. Origa:Novartis: Honoraria; Bluebird Bio: Consultancy; Cerus Corporation: Research Funding; Apopharma: Honoraria. Mufti:Cerus Corporation: Employment, Equity Ownership. Erikson:Cerus Corporation: Employment, Equity Ownership. North:Cerus Corporation: Employment, Equity Ownership. Waldhaus:Cerus Corporation: Employment, Equity Ownership. Ernst:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Huang:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.

Hyperleukocytosis in patients with leukemia is associated with early mortality, especially due to the pulmonary and neurological complications of leukostasis. The prompt use of leukapheresis may improve patients' survival in the initial treatment period. The medical records of all previously untreated acute leukemia patients were reviewed to determine whether there was hyperleukocytosis at presentation. This study summarizes a single-center experience of leukapheresis that was applied to 12 children with acute leukemia and hyperleukocytosis. The median leukocyte count at diagnosis was 589,000/mm(3) (range: 389,000-942,000/mm(3)) for ALL patients and 232,000/mm(3) (range: 200,000-282,000/mm(3)) for AML patients. A central venous catheter (CVC) was inserted, and leukapheresis procedures were repeated at 12-hour intervals. A total of 29 leukapheresis cycles were performed on 12 children. The median number of cycles of leukapheresis required by each patient was two (range: 1-4). The median absolute and percentage reductions in white blood cell (WBC) count after the first cycle of leukapheresis were 113,000/mm(3) (range: 55,000-442,000/mm(3)) and 36% (range: 16-57.4%), respectively. As a laboratory finding, mild hypocalcemia was the most frequently observed complication. No patients developed any other problem related to the procedure. Our results showed that leukapheresis is a safe and effective procedure if performed by experienced staff.