Browsing by Author "Universita degli Studi di Milano"

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    Acute radiation dermatitis in breast cancer: Topical therapy with vitamin E acetate in lipophilic gel base
    (2010-12-23) S. Martella; M. Rietjens; V. Lohsiriwat; R. Lazzari; A. Vavassori; B. A. Jereczek; V. Lazzati; M. C. Leonardi; J. Y. Petit; Istituto Europeo di Oncologia; Mahidol University; Universita degli Studi di Milano
    Background: Radiotherapy can cause adverse skin reactions over the course of their treatment. Currently, management is based on several tropical products although there is no gold-standard approach to prevention and management of radiation toxicity. Method: We report our experience of vitamin E acetate in the treatment of radiation dermatitis in breast cancer patients who experienced grade 4 side effects (according to Radiation Therapy Oncology Group criteria). Results: Clinical management consisted of oral antibiotics and local application of vitamin E acetate and local escarectomy. All of the patients achieved complete re-epithelialization within 40 days. Conclusion: Skin ulceration and necrosis post-radiation may interrupt oncological treatment in breast cancer patients. In acute radiodermatitis with skin necrosis, we propose the use of oral antibiotics together with escarectomy and the application of vitamin E acetate to facilitate the healing process in order to minimize the interruption to the oncological treatment. © the authors; licensee ecancermedicalscience.
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    The aging gut motility decay: May symbiotics be acting as "implantable" biologic pace-makers?
    (2006-06-01) Y. Metugriachuk; F. Marotta; K. Pavasuthipaisit; O. Kuroi; J. Tsuchiya; A. Lorenzetti; E. Fesce; E. Minelli; TMC Hospital; Biokenkyusho Research Laboratory; S. Giuseppe Hospital; Universita degli Studi di Milano; Mahidol University
    Motility recording of small and large intestine was performed in old Wistar rats divided into three groups: (a) standard diet, (b) standard diet plus a symbiotic preparation, and (c) standard diet plus a heat-inactivated symbiotic preparation. SCM-III. significantly increased the myoelectric activity of small intestine and colon (p < 0.01 versus [a] and [c]) paralleling "young" values of 4-month-old rats and increased the spike burst frequency in the proximal-distal colon (p < 0.05). SCM-III significantly increased the frequency and duration of spike bursts in the jejunum, transverse-distal colon, and defecation frequency, while decreasing the intervals of migrating motor complex in the colon (p < 0.01) to "young" values with an increased mRNA expression of VIP (p < 0.05). Gut flora manipulation aimed to modulate myoelectric activity can tentatively help reversing age-related motility decay. © Mary Ann Liebert, Inc.
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    Antimicrobial host defence peptide, LL-37, as a potential vaginal contraceptive
    (2014-01-01) Nopparat Srakaew; Charlene D. Young; Arpornrad Sae-Wu; Hongbin Xu; Krista L. Quesnel; Riccardo Di Brisco; Kessiri Kongmanas; Duriya Fongmoon; Greanggrai Hommalai; Wattana Weerachatyanukul; Susan H. Hall; Yong Lian Zhang; Luigi Panza; Laura Franchini; Federica Compostella; Terry W. Pearson; Robert E. Hancock; Richard J. Oko; Louis S. Hermo; Nongnuj Tanphaichitr; Ottawa Hospital Research Institute; University of Ottawa, Canada; Mahidol University; The University of North Carolina at Chapel Hill; Chinese Academy of Sciences; Universita degli Studi del Piemonte Orientale Amedeo Avogadro, Novara; Universita degli Studi di Milano; University of Victoria; The University of British Columbia; Queen's University, Kingston; McGill University
    STUDY QUESTIONDoes antimicrobial peptide, LL-37, inhibit sperm fertilizing ability?SUMMARY ANSWEROur results indicate that LL-37 inhibits mouse and human sperm fertilizing ability.WHAT IS KNOWN ALREADYLL-37, a cationic antimicrobial peptide, exerts its microbicidal effects through the disruption of microbial cytoplasmic membranes following its interaction with microbial surface anionic phospholipids. ALL-38 (an LL-37 close analogue: LL-37 + Ala at the N-terminus) is produced in the vagina 2-6 h post-intercourse from its precursor hCAP-18, a seminal plasma component. At this time, motile sperm have already swum into the uterine cavity, thus unexposed to ALL-38. Since sperm contain a substantial amount of acidic sulfogalactosylglycerolipid (SGG) on their surface, treatment of sperm with LL-37 may cause their membrane disruption in an analogous manner to that occurring on microbial membranes.STUDY DESIGN, SIZE AND DURATIONMouse/human sperm treated (2-30 min) with LL-37 in a physiological concentration range (up to 10.8 μM) were assessed for SGG-dependent LL-37 binding, and parameters relevant to fertilizing ability, namely motility and intactness of the sperm acrosome and plasma membrane. Ability of mouse sperm to fertilize eggs in vitro was also evaluated. Each study was performed with greater than or equal to three different sperm samples. The efficacy of LL-37 to inhibit sperm fertilizing ability in vivo was determined in female mice (n = 26 each for LL-37 treatment and no treatment), using sperm retrieved from 26 males.PARTICIPANTS/MATERIALS, SETTING, METHODSHuman sperm samples were donated by fertile men. LL-37 was chemically synthesized and was biotinylated for sperm binding studies. Sperm motility was assessed by videomicroscopy and the acrosomal status by Coomassie blue staining of acrosome-intact mouse sperm or the exposure of CD46, an inner acrosomal membrane protein, of acrosome reacted human sperm. Sperm membrane permeabilization/disruption was assessed by the loss of hypo-osmotic swelling response, an incorporation of Sytox Green (a membrane impermeable fluorescent DNA dye), and electron microscopy. Mouse IVF was scored by the presence of two pronuclei in eggs 6 h post-insemination. Ability of mouse sperm to fertilize eggs in vivo was determined by the pregnancy outcome of female mice injected transcervically with sperm with or without LL-37.MAIN RESULTS AND THE ROLE OF CHANCEBiotinylated LL-37 bound to both mouse and human sperm and the binding was partially dependent on sperm surface SGG. Mouse and human sperm became immotile and underwent a premature acrosome reaction upon treatment with LL-37 at 3.6 and 10.8 μM, respectively. The initial action of LL-37 on both mouse and human sperm appeared to be through permeabilization/ disruption of sperm surface membranes evidenced by the loss of hypo-osmotic swelling response, Sytox Green staining and electron microscopy revealing ultrastructural damage. Mouse sperm treated with 3.6 μM LL-37 lost the ability to fertilize eggs both in vitro and in vivo. All 26 female mice inseminated with sperm and LL-37 did not become pregnant. No apparent damage to the reproductive tract was observed as revealed by histological characterization in LL-37-inseminated mice and these females resumed fecundity following mating with fertile males.LIMITATIONS, REASONS FOR CAUTIONDirect demonstration that LL-37 treated human sperm fail to fertilize eggs was limited by legal restrictions on obtaining human eggs for such use.WIDER IMPLICATIONS OF THE FINDINGSOur results reveal selective inhibitory effects of LL-37 on sperm fertilizing ability in mice without apparent impairment to the female reproductive tract. LL-37 is therefore a promising candidate to be developed into a vaginal contraceptive with microbicidal activity.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by Grand Challenges Explorations grant from the Bill & Melinda Gates Foundation (OPP1024509), Canadian Institutes of Health Research (MOP119438 & CCI82413) and International Collaboration and Exchanges NSFC of China (No.30611120525). There are no competing interests to declare. © The Author 2014.
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    Approaching low liver iron burden in chelated patients with non-transfusion-dependent thalassemia: The safety profile of deferasirox
    (2014-01-01) Ali T. Taher; John B. Porter; Vip Viprakasit; Antonis Kattamis; Suporn Chuncharunee; Pranee Sutcharitchan; Noppadol Siritanaratkul; Raffaella Origa; Zeynep Karakas; Dany Habr; Zewen Zhu; M. Domenica Cappellini; American University of Beirut; UCL; Mahidol University; University of Athens; King Chulalongkorn Memorial Hospital, Faculty of Medicine Chulalongkorn University; Ospedale Regional Microcitemie; Istanbul Tip Fakultesi; Novartis Pharmaceuticals; Universita degli Studi di Milano
    Objective: Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload and related complications, and may require iron chelation. However, the risk of over-chelation emerges as patients reach low, near-normal body iron levels and dose adjustments may be needed. In the THALASSA study, the threshold for chelation interruption was LIC <3 mg Fe/g dw (LIC<3); 24 patients receiving deferasirox for up to 2 yr reached this target. A post hoc analysis was performed to characterize the safety profile of deferasirox as these patients approached LIC<3. Methods: THALASSA was a randomized, double-blind, placebo-controlled study of two deferasirox regimens (5 and 10 mg/kg/d) versus placebo in patients with NTDT. Patients randomized to deferasirox or placebo in the core could enter a 1-yr extension, with all patients receiving deferasirox (extension starting doses based on LIC at end-of-core and prior chelation response). The deferasirox safety profile was assessed between baseline and 6 months before reaching LIC<3 (Period 1), and the 6 months immediately before achieving LIC<3 (Period 2). Results: Mean ± SD deferasirox treatment duration up to reaching LIC<3 was 476 ± 207 d, and deferasirox dose was 9.7 ± 3.0 mg/kg/d. The exposure-adjusted AE incidence regardless of causality was similar in periods 1 (1.026) and 2 (1.012). There were no clinically relevant differences in renal and hepatic laboratory parameters measured close to the time of LIC<3 compared with measurements near the previous LIC assessment. Conclusions: The deferasirox safety profile remained consistent as patients approached the chelation interruption target, indicating that, with appropriate monitoring and dose adjustments in relation to iron load, low iron burdens may be reached with deferasirox with minimal risk of over-chelation. © 2014 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.
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    Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead
    (2015-06-01) William H. Goodson; Leroy Lowe; David O. Carpenter; Michael Gilbertson; Abdul Manaf Ali; Adela Lopez de Cerain Salsamendi; Ahmed Lasfar; Amancio Carnero; Amaya Azqueta; Amedeo Amedei; Amelia K. Charles; Andrew R. Collins; Andrew Ward; Anna C. Salzberg; Annamaria Colacci; Ann Karin Olsen; Arthur Berg; Barry J. Barclay; Binhua P. Zhou; Carmen Blanco-Aparicio; Carolyn J. Baglole; Chenfang Dong; Chiara Mondello; Chia Wen Hsu; Christian C. Naus; Clement Yedjou; Colleen S. Curran; Dale W. Laird; Daniel C. Koch; Danielle J. Carlin; Dean W. Felsher; Debasish Roy; Dustin G. Brown; Edward Ratovitski; Elizabeth P. Ryan; Emanuela Corsini; Emilio Rojas; Eun Yi Moon; Ezio Laconi; Fabio Marongiu; Fahd Al-Mulla; Ferdinando Chiaradonna; Firouz Darroudi; Francis L. Martin; Frederik J. Van Schooten; Gary S. Goldberg; Gerard Wagemaker; Gladys Nangami; Gloria M. Calaf; Graeme Williams; Gregory T. Wolf; Gudrun Koppen; Gunnar Brunborg; H. Kim Lyerly; Harini Krishnan; Hasiah Ab Hamid; Hemad Yasaei; Hideko Sone; Hiroshi Kondoh; Hosni K. Salem; Hsue Yin Hsu; Hyun Ho Park; Igor Koturbash; Isabelle R. Miousse; A. Ivana Scovassi; James E. Klaunig; Jan Vondráček; Jayadev Raju; Jesse Roman; John Pierce Wise; Jonathan R. Whitfield; Jordan Woodrick; Joseph A. Christopher; Josiah Ochieng; Juan Fernando Martinez-Leal; Judith Weisz; Julia Kravchenko; Jun Sun; Kalan R. Prudhomme; Kannan Badri Narayanan; Karine A. Cohen-Solal; Kim Moorwood; Laetitia Gonzalez; Laura Soucek; Le Jian; Leandro S. D'Abronzo; Liang Tzung Lin; Lin Li; Linda Gulliver; Lisa J. McCawley; Lorenzo Memeo; Louis Vermeulen; Luc Leyns; Luoping Zhang; Getting to Know Cancer; Lancaster University; University at Albany State University of New York; Getting to Know Cancer; Universiti Sultan Zainal Abidin; Universidad de Navarra; Rutgers Biomedical and Health Sciences; Hospital Universitario Virgen del Rocio; Universita degli Studi di Firenze; University of Reading; Universitetet i Oslo; University of Bath; Penn State College of Medicine; Environmental Protection and Health Prevention Agency; Norwegian Institute of Public Health; National Research Council Canada; University of Kentucky; Centro Nacional de Investigaciones Oncologicas; McGill University; Consiglio Nazionale delle Ricerche; National Center for Advancing Translational Sciences; The University of British Columbia; Jackson State University; University of Wisconsin Madison; Western University; Stanford University School of Medicine; National Institute of Environmental Health Sciences; City University of New York; Colorado State University; The Johns Hopkins School of Medicine; Universita degli Studi di Milano; Universidad Nacional Autonoma de Mexico; Sejong University; Universita degli Studi di Cagliari; University of Kuwait; University of Milano - Bicocca; College of North Atlantic; Maastricht University; Rowan University; Hacettepe Universitesi; Meharry Medical College; Columbia University Medical Center; Universidad de Tarapaca de Arica; University of Michigan Medical School; Flemish Institute for Technological Research; Duke University Medical Center; Universiti Putra Malaysia; Brunel University London; National Institute for Environmental Studies of Japan; Kyoto University Hospital; Cairo University; Tzu Chi University; Yeungnam University; University of Arkansas for Medical Sciences; Indiana University; Academy of Sciences of the Czech Republic; Toxicology Research Division; University of Louisville; Louisville Veterans Administration Medical Center; University of Southern Maine; Vall d`Hebron Institut de Oncologia; Lombardi Comprehensive Cancer Center; University of Cambridge; Department of Cell Biology; Rush University; Oregon State University; The Cancer Institute of New Jersey; Vrije Universiteit Brussel; Institucio Catalana de Recerca I Estudis Avancats; Curtin University; Department of Health Western Australia; University of California, Davis; Taipei Medical University; Chinese University of Hong Kong; University of Otago; Vanderbilt University; Mediterranean Institute of Oncology; Academic Medical Centre, University of Amsterdam; University of California, Berkeley; National Cancer Institute; Universita degli Studi di Napoli Federico II; Centre de recherche en cancérologie de Lyon; United States Army; Istituto Italiano di Tecnologia; California Pacific Medical Center
    © The Author 2015. Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
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    Breast cancer subtype approximations and loco-regional recurrence after immediate breast reconstruction
    (2013-03-01) M. C. Kneubil; J. Brollo; E. Botteri; G. Curigliano; N. Rotmensz; A. Goldhirsch; V. Lohsiriwat; A. Manconi; S. Martella; B. Santillo; J. Y. Petit; M. Rietjens; Istituto Europeo di Oncologia; Universita degli Studi di Milano; Mahidol University
    Background: A small but significant proportion of patients with breast cancer (BC) will develop loco-regional recurrence (LRR) after immediate breast reconstruction (IBR). The LRR also varies according to breast cancer subtypes and clinicopathological features. Methods: We studied 1742 consecutive BC patients with IBR between 1997 and 2006. According to St Gallen conference consensus 2011, its BC approximations were applied to classify BC into five subtypes: estrogen receptor (ER) and/or progesterone receptor (PgR) positive, HER2 negative, and low Ki67 (<14%) [luminal A]; ER and/or PgR positive, HER2 negative and high Ki67(≥14%) [luminal B/HER2 negative]; ER and/or PgR positive, any Ki67 and HER2 positive [luminal B/HER2 positive]; ER negative, PgR negative and HER2 positive [HER2 positive/nonluminal]; and ER negative, PgR negative and HER2 negative [triple negative]. Cumulative incidences of LRR were compared across different subgroups by means of the Gray test. Multivariable Cox regression models were applied. Results: Median follow up time was 74 months (range 3-165). The cumulative incidence of LRR was 5.5% (121 events). The 5-year cumulative incidence of LRR was 2.5% for luminal A; 5.0% for luminal B/HER2 negative; 9.8% for luminal B/HER2 positive; 3.8% for HER2 non luminal; and 10.9% for triple negative. On multivariable analysis, tumor size (pT) >2 cm, body mass index (BMI) ≥25, triple negative and luminal B/HER2 positive subtypes were associated with increased risk of LRR. Conclusion: Luminal B/HER2 positive, triple negative subtypes and BMI ≥25 are independent prognostic factors for risk of LRR after IBR. © 2012 Published by Elsevier Ltd.
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    Congenital afibrinogenaemia caused by uniparental isodisomy of chromosome 4 containing a novel 15-kb deletion involving fibrinogen Aα-chain gene
    (2004-11-01) Silvia Spena; Stefano Duga; Rosanna Asselta; Flora Peyvandi; Chularatana Mahasandana; Massimo Malcovati; Maria Luisa Tenchini; Universita degli Studi di Milano; Mahidol University
    Among rare inherited deficiencies of coagulation factors, congenital afibrinogenaemia is characterised by the lack of fibrinogen in plasma. In the last few years, several genetic defects underlying afibrinogenaemia (mostly point mutations) have been described in the fibrinogen gene cluster. In this study, the molecular basis responsible for afibrinogenaemia in a Thai proband was defined. Point mutation screening was accomplished by directly sequencing the three fibrinogen genes. The impossibility to amplify fibrinogen Aα-chain gene (FGA) exons 5 and 6 suggested the presence of a homozygous deletion. A specific long-range PCR assay enabled the identification of a novel 15-kb deletion, representing the largest afibrinogenaemia-causing deletion described so far. Direct sequencing of the deletion junction allowed mapping of the breakpoints in FGA intron 4 and in the intergenic region between Aα- and Bβ-chain genes. Since the mutation was inherited only from the mother and nonpaternity was ruled out, a maternal uniparental disomy (UPD) was hypothesised. UPD test, carried out with markers covering the whole chromosome 4, revealed that maternal isodisomy was responsible for homozygosity of the 15-kb deletion in the proband. The apparently normal phenotype of the proband, except for afibrinogenaemia, suggests that UPD for chromosome 4 is clinically silent. This represents the first case of a documented complete isodisomy of chromosome 4 causing the phenotypic expression of a recessive disorder. In silico analyses of the regions surrounding the breakpoints suggested that the 15-kb deletion might have originated from an inappropriate repair of a double-strand break by the nonhomologous end joining mechanism. © 2004 Nature Publishing Group All rights reserved.
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    Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload
    (2011-01-01) Dudley J. Pennell; John B. Porter; Maria Domenica Cappellini; Lee Lee Chan; Amal El-Beshlawy; Yesim Aydinok; Hishamshah Ibrahim; Chi Kong Li; Vip Viprakasit; Mohsen Saleh Elalfy; Antonis Kattamis; Gillian Smith; Dany Habr; Gabor Domokos; Bernard Roubert; Ali Taher; Royal Brompton Hospital; UCL; Universita degli Studi di Milano; University of Malaya Medical Centre; Cairo University; Ege University Medical School; Kuala Lumpur Hospital; Prince of Wales Hospital Hong Kong; Mahidol University; Ain Shams University; University of Athens; Novartis Pharmaceuticals; Novartis International AG; American University of Beirut
    Background The efficacy of cardiac iron chelation in transfusion-dependent patients has been demonstrated in one-year prospective trials. Since normalization of cardiac T2* takes several years, the efficacy and safety of deferasirox was assessed for two years in patients with β-thalassemia major in the cardiac sub-study of the EPIC trial. Design and Methods Eligible patients with myocardial T2* greater than 5 to less than 20 ms received deferasirox, with the primary endpoint being the change in T2* from baseline to two years. Results Baseline myocardial T2* was severe ( > 5 to < 10 ms) in 39 patients, and moderate-to-mild (10 to < 20 ms) in 62 patients. Mean deferasirox dose was 33.1±3.7 mg/kg/d in the one-year core study increasing to 36.1±7.7 mg/kg/d during the second year of treatment. Geometric mean myocardial T2* increased from a baseline of 11.2 to 14.8 ms at two years (P < 0.001). In patients with moderate-to-mild baseline T2*, an increase was seen from 14.7 to 20.1 ms, with normalization (≥20 ms) in 56.7% of patients. In those with severe cardiac iron overload at baseline, 42.9% improved to the moderate-to-mild group. The incidence of drug-related adverse events did not increase during the extension relative to the core study and included (≥5%) increased serum creatinine, rash and increased alanine aminotransferase. Conclusions Continuous treatment with deferasirox for two years with a target dose of 40 mg/kg/d continued to remove iron from the heart in patients with β-thalassemia major and mild, moderate and severe cardiac siderosis. © 2011 Ferrata Storti Foundation.
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    Contrast enhanced breast MRI: Spatial displacement from prone to supine patient's position. Preliminary results
    (2012-06-01) Luca Alessandro Carbonaro; Penampai Tannaphai; Rubina Manuela Trimboli; Nicola Verardi; Maria Paola Fedeli; Francesco Sardanelli; IRCCS Policlinico San Donato; Mahidol University; Universita degli Studi di Milano
    Objective: To estimate the spatial displacement of breast lesions and nipples in MR images when the patient is moved from the standard prone to a supine position close to ultrasound (US) or surgical setting. Materials and methods: Eleven patients underwent breast MRI in prone position with dynamic 3D T1-weighted sequences using 0.1 mmol/kg gadobenate dimeglumine. Subsequently, the patient was repositioned in supine position and a 3D volumetric interpolated breathhold examination sequence was acquired using a thoracic surface coil. For both positions we measured the following minimal distances: (A) from lesion margin to the coronal plane passing through the anterior surface of the sternum, antero-posterior, on native axial images; (B) from lesion margin to the medial sagittal plane, on native axial images, latero-medial; (C) from lesion margin to the axial plane passing through the tracheal bifurcation, cranio-caudal; (D) from lesion margin to the thoracic wall/pectoral muscle, on native axial images; (E) from lesion margin to the skin, on native axial images; (F) from lesion margin to the base of the nipple, on oblique reconstructions. Measurements from A t o D were also obtained for each nipple. The prone-to-supine spatial displacement was calculated as the absolute difference between the measurement obtained in supine position and the same measurement obtained in prone position. Displacements were presented as mean ± standard deviation and median in parenthesis. Results: Lesion displacements were (mm): A = 60 ± 38 (55); B = 40 ± 26 (41); C = 41 ± 33 (34); D = 32 ± 31 (27); E = 6 ± 5 (7); and F = 8 ± 6 (7). Nipple displacements were (mm): A = 84 ± 44 (91); B = 54 ± 24 (56); C = 27 ± 15 (24); and D = 48 ± 20 (48). Conclusion: These preliminary results show that preoperative breast MRI in prone position implies a median lesion displacement of about 3-6 cm along the three orthogonal directions in comparison with supine MRI. Conversely, median lesion-to-skin and lesion-to-nipple displacements were less than 1 cm, even though nipple displacements were similar to or larger than those of lesions. The lesion-to-nipple distance may be the most reliable measure to be used for second look breast US. Larger studies are warranted in order to define an optimized breast MRI protocol in the preoperative setting. © 2012 Elsevier Ireland Ltd. All rights reserved.
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    Deferasirox demonstrates a dose-dependent reduction in liver iron concentration and consistent efficacy across subgroups of non-transfusion-dependent thalassemia patients
    (2013-06-01) Ali T. Taher; John B. Porter; Vip Viprakasit; Antonis Kattamis; Suporn Chuncharunee; Pranee Sutcharitchan; Noppadol Siritanaratkul; Renzo Galanello; Zeynep Karakas; Tomasz Lawniczek; Dany Habr; Jacqueline Ros; Yiyun Zhang; M. Domenica Cappellini; American University of Beirut Medical Center; UCL Cancer Institute; Mahidol University; University of Athens; Chulalongkorn University; Ospedale Regional Microcitemie; Istanbul Tip Fakultesi; Novartis International AG; Novartis Pharmaceuticals; Universita degli Studi di Milano
    The 1-year THALASSA study enrolled 166 patients with various non-transfusion-dependent thalassemia (NTDT) syndromes, degrees of iron burden and patient characteristics, and demonstrated the overall efficacy and safety of deferasirox in reducing liver iron concentration (LIC) in these patients. Here, reduction in LIC with deferasirox 5 and 10mg/kg/day starting dose groups is shown to be consistent across the following patient subgroups-baseline LIC/serum ferritin, age, gender, race, splenectomy (yes/no), and underlying NTDT syndrome (β-thalassemia intermedia, HbE/β-thalassemia or α-thalassemia). These analyses also evaluated deferasirox dosing strategies for patients with NTDT. Greater reductions in LIC were achieved in patients dose-escalated at Week 24 from deferasirox 10mg/kg/day starting dose to 20mg/kg/day. Patients who received an average actual dose of deferasirox >12.5-≤17.5mg/kg/day achieved a greater LIC decrease compared with the ≥7.5-≤12.5mg/kg/day and >0-<7.5mg/kg/day subgroups, demonstrating a dose-response efficacy. LIC reduction across patient subgroups was generally consistent with the primary efficacy analysis with a similar safety profile. © 2013 Wiley Periodicals, Inc.
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    Deferasirox effectively reduces iron overload in non-transfusion-dependent thalassemia (NTDT) patients: 1-year extension results from the THALASSA study
    (2013-11-01) Ali T. Taher; John B. Porter; Vip Viprakasit; Antonis Kattamis; Suporn Chuncharunee; Pranee Sutcharitchan; Noppadol Siritanaratkul; Renzo Galanello; Zeynep Karakas; Tomasz Lawniczek; Dany Habr; Jacqueline Ros; Zewen Zhu; M. Domenica Cappellini; American University of Beirut; UCL; Mahidol University; University of Athens; Chulalongkorn University; Universita degli Studi di Cagliari; Istanbul Tip Fakultesi; Novartis International AG; Novartis Pharmaceuticals; Universita degli Studi di Milano
    Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload that requires chelation to levels below the threshold associated with complications. This can take several years in patients with high iron burden, highlighting the value of long-term chelation data. Here, we report the 1-year extension of the THALASSA trial assessing deferasirox in NTDT; patients continued with deferasirox or crossed from placebo to deferasirox. Of 133 patients entering extension, 130 completed. Liver iron concentration (LIC) continued to decrease with deferasirox over 2 years; mean change was -7.14 mg Fe/g dry weight (dw) (mean dose 9.8 ± 3.6 mg/kg/day). In patients originally randomized to placebo, whose LIC had increased by the end of the core study, LIC decreased in the extension with deferasirox with a mean change of -6.66 mg Fe/g dw (baseline to month 24; mean dose in extension 13.7 ± 4.6 mg/kg/day). Of 166 patients enrolled, 64 (38.6 %) and 24 (14.5 %) patients achieved LIC <5 and <3 mg Fe/g dw by the end of the study, respectively. Mean LIC reduction was greatest in patients with the highest pretreatment LIC. Deferasirox progressively decreases iron overload over 2 years in NTDT patients with both low and high LIC. Safety profile of deferasirox over 2 years was consistent with that in the core study. © 2013 The Author(s).
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    Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with β-thalassemia major
    (2012-06-01) Dudley J. Pennell; John B. Porter; Maria Domenica Cappellini; Lee Lee Chan; Amal El-Beshlawy; Yesim Aydinok; Hishamshah Ibrahim; Chi Kong Li; Vip Viprakasit; Mohsen S. Elalfy; Antonis Kattamis; Gillian Smith; Dany Habr; Gabor Domokos; Bernard Roubert; Ali Taher; Royal Brompton Hospital; UCL; Universita degli Studi di Milano; University of Malaya Medical Centre; Cairo University; Ege Universitesi; Kuala Lumpur Hospital; Prince of Wales Hospital Hong Kong; Mahidol University; Ain Shams University; University of Athens; Novartis Pharmaceuticals; Novartis International AG; American University of Beirut
    Background Prospective data on cardiac iron removal are limited beyond one year and longer-term studies are, therefore, important. Design and Methods Seventy-one patients in the EPIC cardiac substudy elected to continue into the 3 rd year, allowing cardiac iron removal to be analyzed over three years. Results Mean deferasirox dose during year 3 was 33.6±9.8 mg/kg per day. Myocardial T2*, assessed by cardiovascular magnetic resonance, significantly increased from 12.0 ms ±39.1% at baseline to 17.1 ms ±62.0% at end of study (P < 0.001), corresponding to a decrease in cardiac iron concentration (based on ad hoc analysis of T2*) from 2.43±1.2 mg Fe/g dry weight (dw) at baseline to 1.80 ±1.4 mg Fe/g dw at end of study (P < 0.001). After three years, 68.1% of patients with baseline T2* 10 to < 20 ms normalized (≥20 ms) and 50.0% of patients with baseline T2* > 5 to < 10 ms improved to 10 to < 20 ms. There was no significant variation in left ventricular ejection fraction over the three years. No deaths occurred and the most common investigator-assessed drugrelated adverse event in year 3 was increased serum creatinine (n=9, 12.7%). Conclusions Three years of deferasirox treatment along with a clinically manageable safety profile significantly reduced cardiac iron overload versus baseline and normalized T2* in 68.1% (32 of 47) of patients with T2* 10 to < 20 ms. © 2012 Ferrata Storti Foundation.
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    Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study
    (2010-09-01) Norbert Gattermann; Carlo Finelli; Matteo Della Porta; Pierre Fenaux; Arnold Ganser; Agnes Guerci-Bresler; Mathias Schmid; Kerry Taylor; Dominique Vassilieff; Dany Habr; Gabor Domokos; Bernard Roubert; Christian Rose; L. Agaoglu; G. Alimena; D. Alonso; S. Ame; E. Angelucci; B. Arrizabalaga; M. Athanasiou-Metaxa; B. Augustson; Y. Aydinok; A. Baba; M. Baccarani; J. Beck; P. Beris; O. Beyne-Rauzy; H. Birgens; D. Bordessoule; C. Borgna-Pignatti; A. Bosly; K. Bouabdallah; D. Bowden; D. Bowen; D. Bron; M. D. Cappellini; M. Capra; G. Cartron; M. Cazzola; C. Chalkias; L. L. Chan; S. Chancharunee; C. Chapman; P. Charoenkwan; E. Chasapopoulou; S. Cheze; A. Chuansumrit; P. Cianciulli; C. Dauriac; M. Delforge; G. Dölken; H. Dombret; J. Duyster; T. Economopoulos; G. Ehninger; M. Elalfy; A. El-Beshlawy; L. Enggaard; G. Fillet; A. Filosa; G. Forni; R. Galanello; G. Gastl; S. Giraudier; A. Goldfarb; A. Grigg; F. Gumruk; S. Y. Ha; D. Haase; B. Heinrich; M. Hertzberg; J. Ho; H. C. Hsu; S. Huang; M. Hunault-Berger; B. Inusa; D. Jaulmes; J. Jensen; A. Kattamis; Y. Kilinc; K. H. Kim; S. Kinsey; L. Kjeldsen; A. Koren; M. E. Lai; Y. Lai; J. W. Lee; K. H. Lee; S. H. Lee; L. Legros; C. Li; C. K. Li; Q. Li; K. H. Lin; W. Linkesch; M. Lübbert; D. Lutz; A. J. Mohamed Thalha; G. Mufti; P. Muus; Heinrich Heine Universitat; Alma Mater Studiorum Universita di Bologna; Universita degli Studi di Pavia; Hopital Avicenne; Medizinische Hochschule Hannover (MHH); Hopital Brabois Adultes; Universitatsklinikum Ulm; Mater Hospital; Universite Paris Descartes; Novartis Pharmaceuticals; Novartis International AG; Hopital Saint Vincent-de-Paul GHICL; Istanbul Universitesi; Azienda Policlinico Umberto I; Hospital Universitario Virgen del Rocio; Hopital de Hautepierre; Azienda Ospedaliera Brotzu - Businco; Hospital de Cruzes; Aristotle University of Thessaloniki; Sir Charles Gairdner Hospital; Ege Universitesi; Hospital Universiti Sains Malaysia; Osp. Bologna; Klinikum der Johannes-Gutenberg-Universitat und Fachbereich Medizin; Hopitaux universitaires de Geneve; Hopital Purpan; Amtssygehusetl Herlev; CHU de Limoges; Az. Ospedaliera Universitaria St. Anna; Cliniques Universitaires UCL; CHU Hopitaux de Bordeaux; Monash Medical Centre; Leeds General Infirmary; Institut Jules Bordet; Universita degli Studi di Milano; Ospedale Civico M. Ascoli; Clinique Victor Hugo; Fondazione IRCCS Policlinico San Matteo; Larissa General Hospital; University of Malaya Medical Centre; Mahidol University; Leicester Royal Infirmary; Chiang Mai University; University Hospitalof Thessaloniki AHEPA; Hopital Clemenceau; Ospedale S. Eugenio; Hopital Pontchaillou; KU Leuven– University Hospital Leuven; Ernst-Moritz-Arndt-Universitat Greifswald; Hopital Saint-Louis; Technical University of Munich; University of Athens Medical School; Dresden University Faculty of Medicine and University Hospital Carl Gustav Carus; Ain Shams University; Cairo University; Hillerod Hospital; Centre Hospitalier Universitaire de Liege; Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli; E.O. Ospedali Galliera; Azienda Ospedaliera Brotzu - Microcitemico; Medizinische Universitat Innsbruck; Hopital Henri Mondor; Hadassah University Medical Centre; Royal Melbourne Hospital; Hacettepe Universitesi; Queen Mary Hospital Hong Kong; Universitatsmedizin Gottingen; Gemeinschaftspraxis Brudler/ Heinrich; Westmead Hospital; Royal Prince Alfred Hospital; Veterans General Hospital-Taipei; Guang Zhou Zhong Shan No.2 Hospital; CHU Angers; Evelina Children's Hospital; Hopital Saint-Antoine; Aarhus Amtssygehus, Aarhus University Hospital; University of Athens; Cukurova Universitesi; Samsung Medical Center, Sungkyunkwan University; St James's University Hospital; Rigshospitalet; Emek Medical Center; Hospital of Nanjing Medical University; The Catholic University of Korea; Asan Medical Center; Royal Adelaide Hospital; Centre Hospitalier Universitaire de Nice, Hopital l'Archet; Nanfang Hospital; Prince of Wales Hospital Hong Kong; Branch of Shanghai No.1 Hospital; National Taiwan University Hospital; LKH-Universitatsklinikum Graz; Universitats Klinikum Freiburg und Medizinische Fakultat; A. Ö. Krankenhausder Elisabethinen; Hospital Universiti Kebangsaan Malaysia; King's College Hospital NHS Foundation Trust; Radboud University Nijmegen Medical Centre
    The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500. ng/mL, ∼50% were chelation-naïve. Overall median serum ferritin decreased significantly at 1 year (p=0.002). Decreases occurred irrespective of whether patients were chelation-naïve or previously chelated; changes were dependent on dose adjustments and ongoing iron intake. Sustained reductions in labile plasma iron were observed. Discontinuation rate (48.7%) and adverse event profile were consistent with previously reported deferasirox data in MDS. Alanine aminotransferase levels decreased significantly; change correlated significantly with reduction in serum ferritin (p<0.0001). This large dataset prospectively confirms the efficacy and well characterizes the safety profile of deferasirox in MDS. © 2010 Elsevier Ltd.
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    Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-Year results from a prospective, randomized, double-blind, placebo-controlled study
    (2012-08-02) Ali T. Taher; John Porter; Vip Viprakasit; Antonis Kattamis; Suporn Chuncharunee; Pranee Sutcharitchan; Noppadol Siritanaratkul; Renzo Galanello; Zeynep Karakas; Tomasz Lawniczek; Jacqueline Ros; Yiyun Zhang; Dany Habr; Maria Domenica Cappellini; American University of Beirut; UCL; Mahidol University; University of Athens; Chulalongkorn University; Universita degli Studi di Cagliari; Istanbul Tip Fakultesi; Novartis International AG; Novartis Pharmaceuticals; Universita degli Studi di Milano
    Nontransfusion-dependent thalassemia (NTDT) patients may develop iron overload and its associated complications despite receiving only occasional or no transfusions. The present 1-year, randomized, double-blind, placebo-controlled THALASSA (Assessment of Exjade in Nontransfusion-Dependent Thalassemia) trial assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients. Atotal of 166 patients were randomized in a 2:1:2:1 ratio to starting doses of 5 or 10 mg/kg/d of deferasirox or placebo. The means ± SD of the actual deferasirox doses received over the duration of the study in the 5 and 10 mg/kg/d starting dose cohorts were 5.7 ± 1.4 and 11.5 ± 2.9 mg/kg/d, respectively. At 1 year, the liver iron concentration (LIC) decreased significantly compared with placebo (least-squares mean [LSM] ± SEM, -2.33 ± 0.7 mg Fe/g dry weight [dw] , P = .001, and -4.18 ± 0.69 mg Fe/g dw, P < .001) for the 5 and 10 mg/kg/d deferasirox groups, respectively (baseline values [means ± SD], 13.11 ± 7.29 and 14.56 ± 7.92 mg Fe/g dw, respectively). Similarly, serum ferritin decreased significantly compared with placebo by LSM -235 and -337 ng/mL for the deferasirox 5 and 10 mg/kg/d groups, respectively (P < .001). In the placebo patients, LIC and serum ferritin increased from baseline by 0.38 mg Fe/g dw and 115 ng/mL (LSM), respectively. The most common drug-related adverse events were nausea (n = 11; 6.6%), rash (n = 8; 4.8%), and diarrhea (n = 6; 3.6%). This is the first randomized study showing that iron chelation with deferasirox significantly reduces iron overload in NTDT patients with a frequency of overall adverse events similar to placebo. © 2012 by The American Society of Hematology.
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    Destabilisation and subsequent lysis of human erythrocytes induced by Plasmodium falciparum haem products
    (2005-04-01) Fausta Omodeo-Salè; Anna Motti; Arjen Dondorp; Nicholas J. White; Donatella Taramelli; Universita degli Studi di Milano; Mahidol University; Churchill Hospital; Facoltà di Farmacia
    In falciparum malaria, both infected and uninfected red cells have structural and functional alterations. To investigate the mechanisms of these modifications, we studied the effects of two Plasmodium falciparum haem products (haematin and malaria pigment in the synthetic form beta-haematin) on isolated human red blood cells (RBCs) and purified RBC ghosts. A dose- and time-dependent incorporation of haematin into RBC ghosts and intact cells was observed, which was in proportion to the extent of haematin- induced haemolysis. RBCs preincubated with haematin were more sensitive to haemolysis induced by hypotonic shock, low pH, H2O2 or haematin itself. Haemolysis was not related to membrane lipid peroxidation and only partially to oxidation of protein sulphydryl groups and it could not be prevented by scavengers of lipid peroxidation or hydroperoxide groups. N-acetylcysteine partly protected the oxidation of SH groups and significantly reduced haemolysis. In contrast, beta-haematin was neither haemolytic nor oxidative towards protein sulphydryl groups. Beta-haematin did destabilise the RBC membrane, but to a lesser extent than haematin, inducing increased susceptibility to lysis caused by hypotonic medium, H2O2 or haematin. This study suggests that the destabilising effect of haematin and, to a much less extent, beta-haematin on the RBC membrane does not result from oxidative damage of membrane lipids but from direct binding or incorporation which may affect the reciprocal interactions between the membrane and cytoskeleton proteins. These changes could contribute to the reduced red cell deformability associated with severe malaria. © Blackwell Munksgaard 2005.
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    Do clinicopathological features of the cancer patient relate with nipple areolar complex necrosis in nipple-sparing mastectomy?
    (2013-03-01) Visnu Lohsiriwat; Nicole Rotmensz; Edoardo Botteri; Mattia Intra; Paolo Veronesi; Stefano Martella; Cristina Garusi; Francesca De Lorenzi; Andrea Manconi; Giuseppe Lomeo; Mario Rietjens; Mario Schorr; Maximiliano Cassilha Kneubil; Jean Yves Petit; Istituto Europeo di Oncologia; Mahidol University; Universita degli Studi di Milano
    Background: The selections of nipple-sparing mastectomy (NSM) are principally depending on oncologic indication and oncologic safety. The main complication of NSM is nipple areolar complex (NAC) necrosis, and it is usually related to surgical technique. However, the patients' clinicopathological factors should be also considered. Method: We retrospectively reviewed 934 consecutive NSM patients during 2002-2007 at the European Institute of Oncology, Milan, Italy. We identified a group of patient who had NAC excision because of NAC necrosis and compared this group with those who had successful NAC conservation. We analyzed the association between the risk of NAC necrosis and the clinicopathological features of the patients. Results: Among 934 NSM, 772 were invasive cancers and 162 were in situ cancers. Of the 934, 40 NAC (4.2 %) were removed during the postoperative period because of necrosis. When we considered age, BMI, menopausal status, smoking status, tumor size, axillary lymph node status, in situ or invasive cancer histology, presence of extensive situ component, grading, estrogen receptor, progesterone receptor, HER2/neu overexpression, Ki-67 proliferative index, and peritumoral vascular invasion, no association was observed between patients' clinicopathological features and NAC necrosis incidence. Conclusions: In our study, clinicopathological features have no significant impact on necrosis complication in therapeutic NSMs. Positive retroareolar margin is the risk of necrosis. Further studies are required to avoid bias due to the different cancer treatments such as different reconstruction techniques and intraoperative radiation protocols. The correlation between breast morphology and NAC necrosis should also be investigated in the future. © 2012 Society of Surgical Oncology.
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    Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme
    (2010-07-01) F. Omodeo-Salè; L. Cortelezzi; Z. Vommaro; D. Scaccabarozzi; A. M. Dondorp; Universita degli Studi di Milano; Mahidol University; Churchill Hospital
    Severe Plasmodium falciparum malaria is associated with hypoargininemia, which contributes to impaired systemic and pulmonary nitric oxide (NO) production and endothelial dysfunction. Since intravascular hemolysis is an intrinsic feature of severe malaria, we investigated whether and by which mechanisms free heme [Fe(III)-protoporphyrin IX (FP)] might contribute to the dysregulation of L-arginine (L-Arg) metabolism and bioavailability. Carrier systems "y+" [or cationic amino acid transporter (CAT)] and "y+L" transport L-Arg into red blood cells (RBC), where it is hydrolyzed to ornithine and urea by arginase (isoform I) or converted to NO•and citrulline by endothelial nitric oxide synthase (eNOS). Our results show a significant and dose-dependent impairment of L-Arg transport into RBC pretreated with FP, with a strong inhibition of the system carrier y+L. Despite the impaired L-Arg influx, higher amounts of L-Arg-derived urea are produced by RBC preexposed to FP caused by activation of RBC arginase I. This activation appeared not to be mediated by oxidative modifications of the enzyme. We conclude that L-Arg transport across RBC membrane is impaired and arginase-mediated L-Arg consumption enhanced by free heme. This could contribute to reduced NO production in severe malaria. Copyright © 2010 the American Physiological Society.
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    Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload
    (2015-06-18) Yesim Aydinok; Antonis Kattamis; M. Domenica Cappellini; Amal El-Beshlawy; Raffaella Origa; Mohsen Elalfy; Yurdanur Kilinç; Silverio Perrotta; Zeynep Karakas; Vip Viprakasit; Dany Habr; Niculae Constantinovici; Junwu Shen; John B. Porter; Ege University Medical School; University of Athens; Universita degli Studi di Milano; Cairo University; Universita degli Studi di Cagliari; Ain Shams University; Cukurova Universitesi; Child and of General and Specialist Surgery; Istanbul Tip Fakultesi; Mahidol University; Novartis Pharmaceuticals; Novartis International AG; UCL Cancer Institute
    © 2015 by The American Society of Hematology. Deferasirox (DFX) monotherapy is effective for reducing myocardial and liver iron concentrations (LIC), although some patients may require intensive chelation for a limited duration. HYPERION, an open-label single-arm prospective phase 2 study, evaluated combination DFX-deferoxamine (DFO) in patients with severe transfusional myocardial siderosis (myocardial [m] T2∗5-<10 ms; left ventricular ejection fraction [LVEF] ≥56%) followed by optional switch to DFX monotherapy when achieving mT2∗>10 ms. Mean dose was 30.5 mg/kg per day DFX and 36.3 mg/kg per day DFO on a 5-day regimen. Geometric mean mT2∗ratios (Gmeanmonth12/24/Gmeanbaseline) were 1.09 and 1.30, respectively, increasing from 7.2 ms at baseline (n = 60) to 7.7 ms at 12 (n = 52) and 9.5 ms at 24 months (n = 36). Patients (17 of 60; 28.3%) achieved mT2∗≥10 ms and ≥10% increase from baseline at month 24; 15 switched to monotherapy during the study based on favorable mT2∗. LIC decreased substantially from a baseline of 33.4 to 12.8 mg Fe/g dry weight at month 24 (-52%). LVEF remained stable with no new arrhythmias/cardiac failure. Five patients discontinued with mT2∗<5 ms and 1 died (suspected central nervous system infection). Safety was consistent with established monotherapies. Results show clinically meaningful improvements in mT2∗in about one-third of patients remaining on treatment at month 24, alongside rapid decreases in LIC in this heavily iron-overloaded, difficult-to-treat population. Combination therapy may be useful when rapid LIC reduction is required, regardless of myocardial iron overload. This trial was registered at www.clinicaltrials.gov as #NCT01254227.
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    Effects of malaria heme products on red blood cell deformability
    (2007-10-01) Forradee Nuchsongsin; Kesinee Chotivanich; Prakaykaew Charunwatthana; Omodeo Salè Fausta; Donatella Taramelli; Nicholas P. Day; Nicholas J. White; Arjen M. Dondorp; Mahidol University; Universita degli Studi di Milano
    In falciparum malaria, the deformability of the entire erythrocyte population is reduced in proportion to disease severity, and this compromises microcirculatory blood flow through vessels partially obstructed by cytoadherent parasitized erythrocytes. The cause of rigidity of uninfected erythrocytes in not known but could be mediated by malaria heme products. In this study, we show that red blood cell deformability (RBC-D), measured by laser-assisted optical rotational cell analyzer, decreased in a dose-dependent manner after incubation with hemin and hydrogen peroxide but not with hemoglobin or β-hematin. Hemin also reduced mean red cell volume. Albumin decreased and N-acetylcysteine (NAC) both prevented and reversed rigidity induced by hemin. Hemin-induced oxidative damage of the membrane seems to be a more important contributor to pathology than cell shrinkage because the antioxidant NAC restored RBC-D but not red blood cell volume. The findings suggest novel approaches to the treatment of potentially lethal malaria. Copyright © 2007 by The American Society of Tropical Medicine and Hygiene.
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    Geographical variations in current clinical practice on transfusions and iron chelation therapy across various transfusion-dependent anaemias
    (2013-01-18) Vip Viprakasit; Norbert Gattermann; Jong Wook Lee; John B. Porter; Ali T. Taher; Dany Habr; Nicolas Martin; Gabor Domokos; Maria Domenica Cappellini; Mahidol University; Heinrich Heine Universitat; The Catholic University of Korea; UCL; American University of Beirut; Novartis Pharmaceuticals; Novartis International AG; Universita degli Studi di Milano
    Background and objectives. Many patients with chronic anaemia require blood transfusions as part of their treatment regimen. As a result, iron overload will inevitably develop if not adequately managed by iron chelation therapy. There are many guidelines relating to transfusion and chelation practices for patients with transfusion-dependent anaemia; however, there is a lack of information on how treatment practices differ around the world. The objective of this manuscript is to highlight key features of current transfusion and chelation management, including similarities and differences across various anaemias and between geographical regions worldwide. Materials and methods. Data collected at study entry to the multicentre Evaluation of Patients' Iron Chelation with Exjade (EPIC) study, which recruited 1,744 patients with a variety of transfusion-dependent anaemias across 23 countries from three geographic regions, were assessed. These analyses compared transfusion and chelation treatment prior to the start of study treatment, together with iron burden assessed at study entry by serum ferritin, liver iron concentration and labile plasma iron levels. Results and conclusions. Data show that transfusion and iron chelation practices differ between anaemias and between geographical regions; this may be linked to availability and accessibility of transfusion and chelation therapy, patients' compliance, physicians' attitudes, costs and use of treatment guidelines. Approximately 60% of these transfusion-dependent patients were severely iron overloaded with a serum ferritin level over 2,500 ng/mL, indicating that the risks of iron burden may have been underestimated and current iron chelation therapy, if considered, may not have been adequate to control iron burden. © SIMTI Servizi Srl.