1.
Iron overload across the spectrum of non-transfusion-dependent thalassaemias: role of erythropoiesis, splenectomy and transfusions.
Porter, JB, Cappellini, MD, Kattamis, A, Viprakasit, V, Musallam, KM, Zhu, Z, Taher, AT
British journal of haematology. 2017;(2):288-299
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Abstract
Non-transfusion-dependent thalassaemias (NTDT) encompass a spectrum of anaemias rarely requiring blood transfusions. Increased iron absorption, driven by hepcidin suppression secondary to erythron expansion, initially causes intrahepatic iron overload. We examined iron metabolism biomarkers in 166 NTDT patients with β thalassaemia intermedia (n = 95), haemoglobin (Hb) E/β thalassaemia (n = 49) and Hb H syndromes (n = 22). Liver iron concentration (LIC), serum ferritin (SF), transferrin saturation (TfSat) and non-transferrin-bound iron (NTBI) were elevated and correlated across diagnostic subgroups. NTBI correlated with soluble transferrin receptor (sTfR), labile plasma iron (LPI) and nucleated red blood cells (NRBCs), with elevations generally confined to previously transfused patients. Splenectomised patients had higher NTBI, TfSat, NRBCs and SF relative to LIC, than non-splenectomised patients. LPI elevations were confined to patients with saturated transferrin. Erythron expansion biomarkers (sTfR, growth differentiation factor-15, NRBCs) correlated with each other and with iron overload biomarkers, particularly in Hb H patients. Plasma hepcidin was similar across subgroups, increased with >20 prior transfusions, and correlated inversely with TfSat, NTBI, LPI and NRBCs. Hepcidin/SF ratios were low, consistent with hepcidin suppression relative to iron overload. Increased NTBI and, by implication, risk of extra-hepatic iron distribution are more likely in previously transfused, splenectomised and iron-overloaded NTDT patients with TfSat >70%.
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Pre-transplantation iron chelation in patients with MDS or acute leukemia and iron overload undergoing myeloablative allo-SCT.
Armand, P, Sainvil, MM, Kim, HT, Rhodes, J, Cutler, C, Ho, VT, Koreth, J, Alyea, EP, Neufeld, EJ, Kwong, RY, et al
Bone marrow transplantation. 2013;(1):146-7
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Efficacy and safety of deferasirox for reducing total body and cardiac iron in thalassemia.
Merchant, R, Ahmed, J, Krishnan, P, Jankharia, B
Indian pediatrics. 2012;(4):281-5
Abstract
OBJECTIVE To assess the efficacy of deferasirox as an iron chelator, with specific reference to reducing cardiac iron overload. DESIGN Prospective, open label, single arm study between 2008-2010. SETUP Thalassemia center at a teaching hospital. PARTICIPANTS 30 multitransfused Thalassemia Major (TM) patients receiving deferasirox (DFX) therapy. METHODS All patients had MRI T2*evaluation for cardiac iron load before starting DFX therapy. MRI T2* was performed on a 1.5 tesla Siemens sonata machine using thalassemia tools software and the ejection fraction measured using standard cardiac magnetic resonance sequence. Quantification of cardiac iron deposit was categorized into T2* <10 ms as high cardiac risk, 10-20 ms as intermediate risk, and >20 ms as low risk. We also estimated left ventricular ejection fraction (LVEF), end systolic volume (ESV) and end diastolic volume (EDV) using standard sequence. EF <56 % was considered to be significant cardiac dysfunction. DFX was administered in an initial dose of 20mg/kg/day and increased to a maximum of 35mg/kg/day. Serum ferritin level was estimated in pretransfusion samples at 1-3 monthly intervals. The primary end point of the study was change in serum ferritin level and cardiac MRI T2* value after 12-18 months therapy. RESULTS Of the 30 patients, cardiac iron value of >20 ms was seen in 15 (50%), whereas 9 (30%; ) had 20-10 ms, and 6 (20%) had <10 ms. The mean serum ferritin pre DFX therapy of all cases was 3859.8 ± 1690.70 ng/mL (1066 - 6725 ng/mL) and mean cardiac T2* was 23.8 ± 15.2 ms (6.24-69.2 ms). After 12 to 18 months of DFX therapy on a mean dose of 33 mg/kg/day, the mean serum ferritin was 2693.4 ± 1831.5 ng/mL (drop by 30.2%, P<0.001) and mean cardiac T2* was 24.2 ± 12.9 ms (increase of 1.6 %, P=0.87). Percentage change in cardiac iron was greater in high risk (24.8%) and intermediate risk (33.4%) patients than low risk patients (8.4%), though these values were not statistically significant. LVEF was 62.0 (± 7.0%) before treatment and changed to 58.9 (± 4.8%) after 18 months of therapy but the values remained within normal range and this change was not significant (P=0.061). Adverse effect of DFX included diarrhea, maculopapular skin rash and transient proteinuria that necessitated temporary stoppage of medication. CONCLUSION Deferasirox monotherapy has a good safety profile and effectively chelates total body iron. It is also a good myocardial iron chelator, more efficacious in moderate to severe cardiac iron overloaded patients.
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[Correction of insulin resistance syndrome does not cause normalisation of hyperferritinaemia].
Roblin, X, Phelip, JM, Hilleret, MN, Heluwaert, F, Bonaz, B, Zarski, JP
Gastroenterologie clinique et biologique. 2003;(12):1079-83
Abstract
UNLABELLED The consequences of iron overload from dysmetabolic hyper-ferritinaemia are a strong motivation for an active medical care program. Venesection therapy is known to be effective in controlling iron overload parameters although no study has evaluated the impact of the normalization of metabolic dysfunction on iron overload. AIMS To evaluate the impact of normalization of metabolic dysfunction on iron overload. METHODS Sixty consecutive patients with dysmetabolic hepatosiderosis were included in a prospective study. Patients with hyper-ferritinaemia above 1000 microg/l were excluded. Multidisciplinary care was offered to all patients to normalize metabolic disorders (body mass index, arterial hypertension, fasting and postprandial hyperglycemia, hyperuricemia, hypercholesterolemia and hypertriglyceridemia) every three months. All patients were followed for one year. At clinical examinations, ferritinaemia concentrations were measured and all dysmetabolic parameters evaluated. MRI was performed at the beginning of the study and at the one year follow-up, to measure hepatic iron load. RESULTS Despite efficient medical care of insulin resistance syndrome, ferritinaemia remained stable. In two thirds of the study population, hyper-ferritinaemia reached at least one and a half times the baseline value, although the dysmetabolic disorders of 40% of the patients were strictly normalized. In this group of 44 patients with strict normalization of metabolic functions, 24 (54%) had hyper-ferritinaemia at one year follow-up whereas 16 other (36%) normalized this parameter. Only 4 patients who had a ferritinaemia below 450 microg/l at baseline, normalized this value at one year. Intra-hepatic iron overload, evaluated by MRI imaging remained stable except for 2 patients who normalized ferritinaemia. CONCLUSION Although efficient handling of dysmetabolic disorders is essential, it is not sufficient to normalize dysmetabolic hyper-ferritinaemia. Only patients with a ferritinaemia value below a baseline of 450 microg/l had normalization of iron overload. Therefore venesection must be offered to all patients with a hyper-ferritinaemia above this value.