Main disorders of iron metabolismIncreased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron deficiency anaemia. In chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, resulting in hypoferraemia and iron restricted erythropoiesis, despite normal iron stores (functional iron deficiency), and finally anaemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD+ID). In contrast, low hepcidin expression may lead to hereditary haemochromatosis (HH type I, mutations of the HFE gene) and type II (mutations of the hemojuvelin and hepcidin genes). Mutations of transferrin receptor 2 lead to HH type III, whereas those of the ferroportin gene lead to HH type IV. All these syndromes are characterised by iron overload. As transferrin becomes saturated in iron overload states, non-transferrin bound iron appears. Part of this iron is highly reactive (labile plasma iron), inducing free radical formation. Free radicals are responsible for the parenchymal cell injury associated with iron overload syndromes.Role of laboratory testing in diagnosisIn iron deficiency status, laboratory tests may provide evidence of iron depletion in the body or reflect iron deficient red cell production. Increased transferrin saturation and/or ferritin levels are the main cues for further investigation of iron overload. The appropriate combination of different laboratory tests with an integrated algorithm will help to establish a correct diagnosis of iron overload, iron deficiency and anaemia.Review of treatment optionsIndications, advantages and side effects of the different options for treating iron overload (phlebotomy and iron chelators) and iron deficiency (oral or intravenous iron formulations) will be discussed.
Iron functions Iron is an essential micronutrient, as it is required for satisfactory erythropoietic function, oxidative metabolism and cellular immune response.
Summary:Iron overload is associated with free radical generation and tissue damage. Our main objective was to ascertain the frequency and severity of iron overload in a group of 59 patients who died after conventional-intensity autologous (n ¼ 24) or allogeneic (n ¼ 35) haematopoietic stem cell transplantation (HSCT). A second objective was to investigate associations between liver-iron concentration and causes of transplant-related mortality. The median age was 41 years (range, 19-66), 41 were males and 18 females. In total, 26 patients had acute leukaemia or MDS, 10 CML, 17 lymphoma, four myeloma and two aplastic anaemia. The median hepatic iron concentration (HIC) was 138 lmol/g dry weight (7.7 mg/g; range 31-631 lmol/g). In total, 4/32 (12%) patients with HIC o150 lmol/g and 10/27 (37%) with hepatic iron X150 lmol/g showed invasive aspergillosis at autopsy (P ¼ 0.035). This was significant in multivariate analysis (RR 9.0; 95% CI 1.6-50.3, P ¼ 0.012). In conclusion, severe iron overload is frequent in patients who die following HSCT and is associated with invasive aspergillosis.
Summary:Iron overload (IO) is associated with free radical generation and tissue damage. Our main objective was to ascertain if very high levels (VHL) of ferritin (у3000 g/l) and transferrin saturation (TS) у100% during conditioning had an impact on overall survival (OS) and transplant-related mortality (TRM) after a haematopoietic stem cell transplantation (HSCT). Levels of ferritin and TS were measured at days ؊7 and ؊4, respectively, in 25 patients who underwent HSCT after CY/TBI. The group consisted of 20 men and five women with a median age of 40 years. Fifteen patients were autotransplanted and 10 allotransplanted. Nine of them had a diagnosis of AL, six of CML and 10 of lymphoma. Thirteen of them were in early and 12 in advanced status of disease. VHL of ferritin and TS у100% were associated with a decreased OS (P ؍ 0.001 and P ؍ 0.006, respectively) and an increased TRM (P ؍ 0.003 and P ؍ 0.004, respectively) in univariate survival analysis. Both variables remained significant at multivariate analysis for OS (P ؍ 0.03 and 0.02, respectively) and TS was an independent factor for TRM (P ؍ 0.01). Ferritin was very close to achieving statistical significance for TRM (P ؍ 0.06) in multivariate analysis. In conclusion, VHL of ferritin and TS у100% at conditioning are associated with an increase in toxic deaths after transplant. Bone Marrow Transplantation (2002) 29, 987-989. DOI: 10.1038/sj/bmt/1703570 Keywords: iron; transferrin saturation; ferritin; survival; TRM; HSCT Iron overload (IO) is associated with free radical production and tissue damage in different diseases such as genetic haemochromatosis and secondary IO. 1,2 IO may be present among patients who undergo haematopoietic stem cell transplantation (HSCT) due to prior blood transfusions. Pre-transplant iron status may be evaluated measuring ferritin levels pre-conditioning; that is a time when ferritin is still neither increased as an acute phase reactant nor influenced by liver toxicity secondary to chemo-radiotherapy. Moreover, transferrin saturation (TS) increases during chemo-radiotherapy, often reaching indexes of over 80% and producing non-transferrin-bound iron (NTBI). 3,4 TS might inform us about the potentially toxic effect of free iron, without any protein control, produced during conditioning. It is likely that an IO status pre-conditioning with an elevated TS during this procedure for HSCT may increase the toxic effects of chemo-radiotherapy. 5 This could cause an increase in transplant-related mortality (TRM) and a subsequent decrease in overall survival (OS). The aim of this study was to determine whether a very high level of ferritin pre-conditioning and/or a full TS during CY-TBI were independent risk factors for TRM and OS. Patients and methodsTwenty-five consecutive patients who underwent HSCT with CY/TBI were prospectively enrolled in the study. All patients were conditioned with cyclophosphamide 60 mg/kg once daily i.v. on days Ϫ6 and Ϫ5 (total dose 120 mg/kg) and TBI 6 ϫ 2 Gy from days Ϫ3 to Ϫ1. GVHD prophylaxis in...
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