Leptin Is Associated with the Degree of Anemia and the Erythropoietin Levels in β Thalassemia Patients

Abstract Background: β-thalassemia (BT) is a hereditary hemolytic anemia. The imbalance between α- and β-globin chain synthesis results in ineffective erythropoiesis, severe microcytic hypochromic anemia and iron overload. Although regular transfusions and iron-chelation therapy markedly improve the survival and quality of life of BT patients, they have also led to the emergence of previously unrecognized complications. Patients with thalassemia major often present with endocrine abnormalities due to dysfunction of the hypothalamic-pituitary axis (Poggi, 2016), and are frequently underweight with abnormally low body-fat percentage (Fung, 2010). Adipose tissue stores lipids, but it also has an endocrine function through the production of leptin, an adipocyte-derived hormone that regulates food intake, metabolic and endocrine functions by activating its receptor in the central nervous system. Leptin plays a regulatory role in immunity and inflammation, and also seems to act synergistically with erythropoietin on mammalian hematopoiesis (Bennett, 1996). For example, a stimulatory effect of leptin on erythropoiesis among patients with end-stage renal disease was observed (Axelsson 2005). Previous studies on leptin in BT patients have shown lower levels than in healthy controls, and a negative correlation with the level of soluble transferrin receptor in transfused patients (Dedoussis, 2002). The reduced leptin levels were explained by a possible toxic effect of iron on adipocytes (Chaliasos, 2010). Study aims: In this study, we investigated the correlation between leptin level and anthropometric parameters in BT patients compared to heathy controls. We also explored the relationship between leptin and hematological and erythropoietic parameters, as well as iron-overload status in BT patients. Patients and methods: Transfusion-dependent BT patients (n = 33; 16 females, 17 males, mean age 23.5 ± 8.6 [range 8-41] years), treated at the Pediatric Hematology Unit of Emek Medical Center, and 11 healthy controls (6 females, 5 males, mean age 26.4 ± 10.4 [range 8-39] years) were studied. Patients were treated by regular blood transfusions and iron-chelation therapy. Anthropometric assessments included height, weight, fat percentage and BMI calculation. Blood samples were obtained at fasting and before blood transfusion. Serum leptin, complete blood count, hemoglobin and reticulocyte counts and serum erythropoietin were analyzed. These studies were performed twice, 3 months apart, and the mean values were utilized for the statistical analysis. Serum leptin levels were analyzed by radioimmunoassay, and leptin-normalized values were calculated (ng/dL leptin per % body fat). Results: BT patients were found to have lower leptin levels than healthy controls (5.4 ± 5.9 vs. 13 ± 10.1 ng/dL; p= 0.0006). Leptin levels were higher in females than in males (mean leptin 7.2 ± 6.5 vs. 3.7 ± 4.7 ng/dL; p= 0.01), and increased with age (r= 0.4635, p= 0.0066). A negative correlation was found between leptin and erythropoietin (r= -0.43473, p= 0.0115), and a positive correlation between leptin and hemoglobin, as well as the mean pre-transfusion hemoglobin levels in the previous 5 years (r= 0.66884, p < 0.001; r= 0.40261, p= 0.0202, respectively). No correlation was observed between leptin levels and anthropometric parameters (weight, height, BMI), iron-overload parameters or reticulocyte count. Fasting and normalized leptin showed similar patterns. Conclusions: This study confirms that BT patients are unable to maintain adequate leptin production, suggesting that adipose tissue dysfunction may be related to the chronic anemia. Our results correlate well with previous studies of lower leptin levels in BT patients. The positive correlation of leptin level with hemoglobin, together with the inverse correlation with erythropoietin provide further evidence of the effect of leptin on erythropoiesis. Additional studies are needed to examine the intricate interplay between adipose tissue, leptin and erythropoiesis in the environment of chronic anemia and iron overload present in BT patients. Disclosures No relevant conflicts of interest to declare.

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Effective and Safe Deferasirox Treatment of Patients with Various anemia's and Transfusional Iron-Overload in the Medical Practice: Results From Two German Observational Studies

Blood ◽

10.1182/blood.v118.21.5165.5165 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5165-5165

Author(s):

Christian Junghanss ◽

Rudolf Schlag ◽

Bernd Gaede ◽

Matthias Moelle ◽

Steffen Doerfel ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Observational Studies ◽

Chelation Therapy ◽

Iron Chelation ◽

Iron Chelator ◽

Beta Thalassemia ◽

Final Visit ◽

Iron Chelation Therapy ◽

The Mean

Abstract Abstract 5165 Background: Progressive anaemia is highly prevalent amongst many malignant diseases leading to RBC transfusion-dependency. Therefore transfusion-related iron overload (IOL) is common in these patients (pts) and can result in multiple organ failure. Iron chelation therapy prevents organ failure, reduces the risk of infections and can improve hematopoesis in some diseases. The once-daily oral iron chelator deferasirox has been shown to reduce iron overload in pts with various transfusion-dependent anaemias assessed by serum ferritin (SF). Despite extensive knowledge of iron chelation in MDS or beta-thalassemia pts, data in pts with other anaemias is limited. Here, we present data from a subgroup of transfusion-related IOL pts that were included two non-interventional studies (EXTEND, EXJANGE) performed in Germany and who suffered from diseases other than MDS or beta thalassemia. Methods: 130 pts with various malignant diseases such as myeloproliferative disorders (43 pts, including 31 pts particular specified as myelofibrosis), acute myeloid leukaemia (14 pts), sickle cell anaemia (6 pts), aplastic anaemia (11), congenital aplastic anaemia (5) or Non-Hodgkin's lymphoma (6 pts) were treated with deferasirox in the daily-routine setting of office-based physicians and included in either the EXTEND or EXJANGE study. Patient with MDS or beta-thalassemia were also included in the studies, but are excluded from this analysis. Analysis is based on 1-year pooled data of these two, multicenter, non-interventional observational studies. Transfusion-dependent pts with IOL with or without prior chelation were enrolled and received the iron chelator deferasirox. Prescription of deferasirox, just as inclusion and exclusion criteria was in accordance with the terms of Exjade marketing authorization in the EU. Efficacy and safety parameters, including serum ferritin and adverse events (AEs), were collected in 2-monthly intervals. Results: 98 pts had no prior chelation therapy (51 M, 45 F, 2 missing; mean age 63.3, range 3.2–91.9 yrs) and a median baseline SF of 2,968 (range 561–11, 423) ng/mL. 32 pts had prior received prior chelation therapy (mainly with desferal; 17 M, 15 F; mean age 50.1, range 3.5–80.9 yrs) and a median baseline SF of 2,635 (range 539–19, 540) ng/mL. The mean number of prior red blood cell transfusions was 55. The mean prescribed daily dose of deferasirox at the first visit was 16.3 mg/kg/d rising up to 18.1 mg/kg/d after 12 months. During treatment, median SF levels clearly decreased from first to final visit [-806 ng/mL; p<0.0001 (explorative analysis)] in the chelation-naïve and also in the pre-chelated population [-300 ng/ml; p = 0.1705 (explorative analysis)]. The median observation period and days on therapy was 349 and 343 days, respectively. At final visit 74 pts (56.9%) were still on deferasirox therapy. Reasons for discontinuation by the final visit included 19 AEs (35.2%). 45 pts (34.6%) experienced an investigator assessed drug-related AE. The most common drug-related AEs were diarrhea (n=17; 37.8%), nausea (n=11; 24.4%) and blood creatinine increased (n=6; 13.3%). As in previous clinical trials, serum creatinine clearances showed a minor decrease over the study period (median decrease until final visit: 4 ml/min). Conclusion: Our analysis confirmed that deferasirox is effective and well tolerated in chelation-naïve as well as in previously chelated pts with transfusion-related IOL and diseases other than MDS or beta thalassemia. As baseline serum ferritin values were >2,500 ng/mL even in pts with prior chelation therapy, adequate chelation treatment should be considered earlier at a serum ferritin >1,000 ng/mL in pts with transfusion-dependent IOL for adequate iron chelation therapy. Disclosures: Junghanss: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Haus:Novartis Pharma: Employment. Junkes:Novartis: Employment. Leismann:Novartis: Employment.

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PATTERN AND CLINICAL PROFILE OF PATIENTS WITH Β- THALASSEMIA IN REPEATED BLOOD TRANSFUSION

10.36106/ijar/7211096 ◽

2020 ◽

pp. 32-34

Author(s):

Ashok Badakali ◽

Deepti Shetty ◽

Manohar MR

Keyword(s):

Blood Transfusion ◽

Iron Overload ◽

Serum Calcium ◽

Chelation Therapy ◽

Iron Chelation ◽

Serum Phosphate ◽

Clinical Profile ◽

Beta Thalassemia ◽

Serum Phosphate Level ◽

The Mean

Chronic transfusions inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemia patients, but with complications like hypocalcaemia. Hence, present study was undertaken to determine pattern and clinical profile of patients with β- thalassemia who are receiving repeated blood transfusion Methods: Hospital based study conducted at S. Nijalingappa Medical College and Hanagal Shri Kumareshwar hospital, Bagalkot. The study period was one and half year from 2015 to 2016. 53 beta thalassemia major cases fulfilling inclusion criteria were investigated after an informed consent, for serum calcium, serum phosphorous, serum ALP and paratharmone levels. Result: Among 53 transfusion dependent children studied, the mean age is 5.249 years. The study consisted of 32 (60.4%) males and 21 (39.6%) females. Maximum number of cases i.e. 29 (54.7%) were diagnosed at the age of 4-6 months. 50 (94.3%) were on iron chelation therapy. The mean serum calcium is 8.28 + 0.89 mg/dl. The mean serum phosphate is 6.40 + 0.80mg/dl, mean PTH is 14.96 + 15.49ng/L. The mean value of serum phosphate level is 14.96 + 15.49 ng/L. The mean ALP is 166.789 U/L. Conclusion: To get better results, regular testing is needed to detect the complications of the early stages with proper treatment of the factors and complications. Therefore, should be monitored to avoid complication related to hypocalcemia.

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Serum Ferritin Elevation and Use of Iron Chelation In Chronically Versus Sporadically Transfused Sickle Cell Patients

Blood ◽

10.1182/blood.v116.21.2671.2671 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2671-2671

Author(s):

Ismael Shaukat ◽

Faraz Khan ◽

Andrew Eisenberger ◽

Marcus Stevenson ◽

Alice J. Cohen

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Renal Dysfunction ◽

Sickle Cell ◽

Serum Ferritin ◽

Chelation Therapy ◽

Iron Chelation ◽

Iron Chelation Therapy ◽

Cell Disease ◽

The Mean

Abstract Abstract 2671 Background: Red cell transfusions play an integral role in the treatment and prevention of serious complications related to sickle cell disease. It has been shown that in other hemoglobinopathies, such as β-Thalassemia, patients (pts) suffer from iron overload which can result in end organ damage. There is concern that heavily transfused sickle cell pts may also develop iron overload with consequent morbidity and mortality. While pediatric pts routinely receive blood transfusions and iron chelation therapy, adult pts often discontinue chronic transfusion programs and are transfused sporadically. These pts may not receive routine iron chelation therapy. Methods: A retrospective review of our sickle cell database from 1988–2010 which also included those pts who were not routinely followed at the comprehensive sickle cell clinic. Adult pts (>18 yrs of age) with serum ferritin (SF) levels >1000 ng/ml (criteria for iron overload in our institution) were identified and use of iron chelation was reviewed in this population. Clinical characteristics evaluated were age, type of sickle cell disease, frequency of transfusions (chronic vs. sporadic), total units transfused, use and type of chelation, as well as reasons for non-use of chelation therapy. Results: 65/170(38%) pts were identified with SF >1000. The mean age is 33 years (range 19–70). 38/65 (59%) have the SS phenotype, 25/65 (38%) have the Sβ phenotype and 2/65 (3%) have the SC phenotype. The mean SF is 3697 ng/ml (range 1012–14312). Of those pts considered to have iron overload, 28/65 (43%) were treated with iron chelation: 27/65 (42%) received deferasirox and 1/65 (2%) received deferoxamine. Of the untreated pts, 24/37 (65%) had no identifiable reason for lack of chelation therapy, 10/37 (27%) had renal dysfunction, 1/37(3%) had hepatic impairment. 16/65 (25%) were transfused chronically, while 49/65 (75 %) were transfused sporadically. Chronically transfused pts received a mean of 81 units throughout their lifetime, while sporadically transfused pts received 30 units (p=0.01). The mean SF for chronically transfused pts was 5891, while the mean SF for pts transfused sporadically was 2981 (p=0.01). Of pts transfused chronically, 11/16 (69%) were on chelation therapy. Of the pts receiving sporadic transfusions, only 16/49 (33%) were on iron chelation (p= 0.01). In all pts chronically transfused, the reason for non-use of chelation therapy was renal dysfunction. In sporadically transfused pts, 33/49 (51%) had no identifiable reason for lack of chelation therapy. Conclusion: SF levels are significantly lower in pts who are sporadically transfused, though levels are high. Adult pts receiving sporadic transfusions are not routinely receiving iron chelation therapy despite elevated SF. The need for chelation therapy in both sporadically and chronically transfused pts remains to be determined. Disclosures: No relevant conflicts of interest to declare.

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Progression of Liver Fibrosis Can be Controlled Under Adequate Chelation in Transfusion-Dependent Thalassemia (TDT).

Blood ◽

10.1182/blood.v128.22.3632.3632 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3632-3632

Author(s):

Diletta Maira ◽

Elena Cassinerio ◽

Alessia Marcon ◽

Marta Mancarella ◽

Mirella Fraquelli ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Iron Overload ◽

Board Of Directors ◽

Chelation Therapy ◽

Liver Stiffness ◽

Iron Chelation ◽

Advisory Committees ◽

Number Of Patients ◽

The Mean

Abstract BACKGROUND. A substantial proportion of patients with transfusion-dependent beta-thalassemia major suffer from chronic liver disease. Iron overload resulting from repeated transfusions and HCV infection have been implicated in the development of liver fibrosis. The objective of iron chelation is to avoid the complications of siderosis, such as hepatocellular injury. As a matter of fact, adequate chelation therapy is mandatory in order to prevent liver disease progression. In the last few years the availability of different chelating agents (coupled with anti-HCV therapy) allowed control of liver disease due to secondary iron overload. Transient elastography (TE, Fibroscan®) is a non-invasive and rapid diagnostic tool that enables accurate prediction of hepatic fibrosis by measuring liver stiffness (LSM). Patients with TDT could benefit from regular non-invasive assessment of liver fibrosis as an indirect indicator of treatment adequacy and therapeutic compliance. AIM. We investigated the efficacy of adequate iron chelation to prevent the progression of liver fibrosis in TDT patients over a time period of approximately 4 years. MATERIALS AND METHODS. We analysed data in a retrospective cohort study over a 4±1.5-year time period. Ninety-nine patients with beta-thalassemia major (41 M, 58 F, aged 36±6 years), followed at Rare Disease Center, Ca' Granda Hospital in Milan, were enrolled in the study. All patients received regular transfusions every 2-4 weeks. Chelation therapy was registered using deferasirox (DFX), deferoxamine (DFO), deferiprone (DFP) or a combination of the three. All the participants underwent TE and T2-weighted magnetic resonance imaging (T2*MRI) twice (at baseline,T0 and after approximately 4 years, T1). Liver iron concentration (LIC) was assessed by T2*MRI using the appropriate formula at T0 and T1. LSM was measured according to the following cut-off: <5.0 kPa no fibrosis (F0), 5.1-7.9 kPa mild fibrosis (F1), >7.9 kPa moderate fibrosis (F2), >10.3 advanced fibrosis (F3), >11.9 kPa cirrhosis (F4). We divided our cohort into groups depending on the administered chelating agent and the presence of iron overload defined by a LIC > 4.23 mg Fe/g dry weight (corresponding to a T2* value > 6.3 ms). RESULTS. At baseline the mean pre-transfusion Hb levels was 9.74 ± 1.17 g/dL, the mean iron intake 0.33 ± 0.07 mg Fe/kg/d and median serum ferritin 669.5 ng/ml (range 113-5912). HCV-RNA positivity was found in 33 patients (33%) at T0: 20 patients were treated for hepatitis C during the observation period. The overall mean LSM was 7.4±3.2 kPa, the mean hepatic T2* was 9.92±7.01 ms and the mean LIC was 4.81±3.82 mg/g dw (n=99). Data available at 4±1.5 years showed a significant reduction in liver stiffness (6.6±3.2 kPa, p 0.017), iron overload measured by hepatic T2* (12.84±7.28 ms, p < 0.001) and LIC (3.65±3.45 mg/g dw, p 0.001). This result was confirmed when considering patients with iron overload at the time of the first measurment (n=41). The number of patients with moderate to advanced fibrosis (LSM ≥ F2) decreased, yet not significantly (30% vs 19%, p 0.07). Subjects treated with a stable dose of DFX over the entire period of observation (n=39) showed a reduction of LSM (6.9±2.3 vs 6.06±2.4, p 0.04) and a concomitant improvement of hepatic T2* and LIC values (respectively 11.02±6.57 vs 15.04±6.42 and 3.84±2.81 vs 2.49±1.89, p < 0.001). In this group we observed a substantial decrease in the number of patients with LIC > 4.23 mg Fe/g dw (33% vs 13%, p 0.01). A reduction of LSM, yet not statistically significant due to the limited size of the cohort, was achieved in patients on combined DFO+DFP at T0 and T1 (n=6, 8.6±5.5 vs 7.3±3.8). The group of patients on DFO (n=11) remained stable over time. Patients who underwent anti-HCV therapy showed an even more evident reduction in LSM (9±3 vs 7±3.1, p 0.016). CONCLUSION. These data support evidence on the efficacy of adequate iron chelation therapy and, if necessary, anti-HCV treatment in decreasing or at least controlling the progression of liver fibrosis measured by TE in transfusion-dependent BTM patients. Therapeutic compliance and tailoring of drugs is essential to prevent hepatic injury resulting from siderosis. Moreover, proper chelation and treatment of HCV infection act sinergistically to limit progression of liver disease in TDT patients with active hepatitis C, so that development of cirrhosis could be either prevented or greatly delayed. Disclosures Cappellini: Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genzyme-Sanofi: Membership on an entity's Board of Directors or advisory committees.

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Iron Chelation Therapy in CAPD: A New and Effective Treatment of Iron Overload Disease in Esrd Patients

Peritoneal Dialysis International ◽

10.1177/089686088300300214 ◽

1983 ◽

Vol 3 (2) ◽

pp. 99-101 ◽

Cited By ~ 13

Author(s):

Glen H Stanbaugh ◽

A. W, Holmes Diane Gillit ◽

George W. Reichel ◽

Mark Stranz

Keyword(s):

Peritoneal Dialysis ◽

Iron Overload ◽

End Stage Renal Disease ◽

Chelation Therapy ◽

Iron Chelation ◽

Iron Chelation Therapy ◽

Peritoneal Dialysate ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

A patient with end-stage renal disease on CAPD, and with massive iron overload is reported. This patient had evidence of myocardial and hepatic damage probably as a result of iron overload. Treatment with desferoxamine resulted in removal of iron in the peritoneal dialysate. On the basis of preliminary studies in this patient it would appear that removal of iron by peritoneal dialysis in conjunction with chelation therapy is safe and effective. This finding should have wide-ranging signficance for patients with ESRD.

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Endocrine complications

Thalassemia Reports ◽

10.4081/thal.2018.7479 ◽

2018 ◽

Vol 8 (1) ◽

Author(s):

Vincenzo De Sanctis

Keyword(s):

Iron Overload ◽

Chelation Therapy ◽

Membrane Lipids ◽

Survival Rates ◽

Iron Chelation ◽

Thalassemia Major ◽

Cellular Iron ◽

Active Iron ◽

Bone Changes ◽

Endocrine Complications

More than five decades ago, thalassemia major (TM) was fatal in the first decade of life. This poor prognosis changed since the survival rates started to increase progressively thanks to the implementation of continuous and significant improvement of diagnostic and therapeutic methods, consisting mainly of an intensive transfusion program combined with chelation therapy and imaging methods. Regular red blood cell (RBC) transfusions eliminate the complications of anemia, compensatory bone marrow expansion, bone changes and splenomegaly, restore the physiological growth throughout childhood and extend survival. The most serious disadvantage of life-saving transfusions is the inexorable accumulation of iron within tissues. Iron is physiologically stored intracellularly in the form of ferritin, a protein whose synthesis is induced upon the influx of iron. When the storage capacity of ferritin is exceeded, pathological quantities of metabolically active iron are released intracellularly in the form of hemosiderin and free iron within an expanded labile pool. This metabolically active iron catalyzes the formation of free radicals, which damage membrane lipids and other macromolecules, leading to cell death and eventually organ failure. Other factors contributing to the variability of cellular iron overload are: a) the cell surface transferrin receptors and the capacity of the cells to deploy defence mechanisms against inorganic iron; b) individual susceptibility to iron toxic effect; c) the development of organ(s) damage secondary to persisting severe iron overload in the years preceding iron chelation therapy; and d) liver disorders, chronic hypoxia and associated endocrine complications. Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications mainly due to iron overload, anemia, and chronic liver disease, which require prompt diagnosis, treatment and close follow-up by specialists.

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Iron Chelation and Ferritin below 500 Mcg/L in Transfusion Dependent Thalassemia: Beyond the Limits of Clinical Trials

Blood ◽

10.1182/blood-2019-130237 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3542-3542 ◽

Cited By ~ 1

Author(s):

Natalia Scaramellini ◽

Carola Arighi ◽

Alessia Marcon ◽

Dario Consonni ◽

Elena Cassinerio ◽

...

Keyword(s):

Clinical Practice ◽

Liver Function ◽

Iron Overload ◽

Board Of Directors ◽

Chelation Therapy ◽

Iron Chelation ◽

Published Data ◽

Iron Chelation Therapy ◽

Iron Intake ◽

Advisory Committees

Introduction The current therapeutic management of transfusion dependent thalassemia (TDT) is based on regular blood transfusion and iron chelation therapy. Transfusion iron overload remains one of the major causes of morbidity and mortality in these patients because of the accumulation in heart, liver and endocrine glands. Three iron chelators are available in clinical practice: deferoxamine (DFO), deferiprone(DFP) and deferasirox (DFX). Guidelines clearly recommend when to start iron chelation, while discontinuation criteria are not well defined. Authorised product information state that we should consider interrupting DFX if serum ferritin (SF) falls consistently below 500mcg/L. This cut off was arbitrarily determined and there are no studies evaluating the effects of chelators in presence of SF below 500 mcg/L. In our clinical practice at Rare Diseases center of Fondazione IRCCS Ca' Granda Policlinico in Milan we do not completely interrupt iron chelation in TDT patients for SF levels below 500 mcg/L. Aims and methods Aim of our study was to evaluate the appearance of adverse events due to the assumption of iron chelation therapy in those TDT patients who had SF below 500 mcg/L. In this study we retrospectively evaluated renal and liver function from 2008 throughout December 2018 in TDT patients on DFX who presented SF below 500 mcg/L for 24 consecutive months. DFX dose are all expressed with the new tablets formulation dose. We evaluated SF, iron intake, LIC and MIC, renal and hepatic function. .A total of 5076 observations were collected, with 99.5 average per patient. We evaluated the relationships among variables with correlation models with random intercept Results One hundred ninety-two TDT patients are regularly followed at our center. They receive regular transfusion treatment and iron chelation therapy to prevent secondary iron overload. 51 out of 192 patients (32 F, 19 M, aged 44 ± 7 years) treated with DFX presented mean SF below 500 mcg/L for at least 24 consecutive months. Hematological and iron status parameters are described in Table 1. We found a strong correlation between SF and LIC (p<0.001) and for SF<500 mcg/L no hepatic iron overload was observed. Conversely we did not found a correlation between SF and MIC. For SF values below 500 mcg/L there was a minimal increase in creatinine levels, however the mean creatinine values remained within the normal range.Moreover, creatinine variation between two consecutive evaluation was below 0.3 mg/dl, cut off for acute kidney injury. Similar results were observed for liver function. Although a minimal increase of mean ALT value was observed for SF below 500 mcg/L, it remained within the normal range. None of our patient showed ALT level indicative of liver damage (ALT> 10 x upper limit of normal) We evaluated the relation between SF and DFX dose. Mean DFX dose decreases according to SF reduction. However, for SF value < 240 mcg/L, DFX dose remained stable at an average of 14 mg/kg per day. Conclusion According to our preliminary data, administration of DFX in TDT patients in presence of SF below 500 mcg/L is safe. Creatinine and ALT fluctuations, that usually remain within the range of normality, are mild, and transient and do not require specific treatment. Consistently with previously published data by Cohen et al, we show that a mean dosage of DFX of 14 mg/Kg die of film-coated tablet (20 mg/Kg of dispersable formulation) are necessary to balance an iron intake of 0.3 mg/kg die in absence of iron overload. Based on these results we suggest that in TDT patients with a continuous iron intake, iron chelation should be continued even when ferritin is below 500mcg/L. Monitoring of liver and kidney function tests are recommended in patient's follow up, as well as tailoring iron chelation. Disclosures Cappellini: Vifor Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria; Novartis: Membership on an entity's Board of Directors or advisory committees; Genzyme/Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Motta:Sanofi-Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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