Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: a report from the Multi-Center Study of Iron Overload

The Children's Hospital of Philadelphia, Filadelfia, Pennsylvania, United States
American Journal of Hematology (Impact Factor: 3.8). 04/2007; 82(4):255-65. DOI: 10.1002/ajh.20809
Source: PubMed


A natural history study was conducted in 142 Thalassemic (Thal), 199 transfused Sickle Cell Disease (Tx-SCD, n = 199), and 64 non-Tx-SCD subjects to describe the frequency of iron-related morbidity and mortality. Subjects recruited from 31 centers in the US, Canada or the UK were similar with respect to age (overall: 25 +/- 11 years, mean +/- SD) and gender (52% female). We found that Tx-SCD subjects were hospitalized more frequently compared with Thal or non-Tx-SCD (P < 0.001). Among those hospitalized, Tx-SCD adult subjects were more likely to be unemployed compared with Thal (RR = 1.6, 95% CI 1.0-2.5) or non-Tx-SCD (RR = 3.1, 95% CI 1.3-7.3). There was a positive relationship between the severity of iron overload, assessed by serum ferritin, and the frequency of hospitalizations (r= 0.20; P = 0.009). Twenty-three deaths were reported (6 Thal, 17 Tx-SCD) in 23.5 +/- 10 months of follow-up. Within the Tx-SCD group, those who died began transfusion (25.3 vs. 12.4 years, P < 0.001) and chelation therapy later (26.8 vs. 14.2 years, P = 0.01) compared with those who survived. The unadjusted death rate in Thal was lower (2.2/100 person years) compared with that in Tx-SCD (7.0/100 person years; RR = 0.38: 95% CI 0.12-0.99). However, no difference was observed when age at death was considered. Despite improvements in therapy, death rate in this contemporary sample of transfused adult subjects with Thal or SCD is 3 times greater than the general US population. Long term follow-up of this unique cohort of subjects will be helpful in further defining the relationship of chronic, heavy iron overload to morbidity and mortality.

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Available from: Samir K Ballas, Oct 23, 2014
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    • "Presence of iron in the body is essential as it forms an important component of metabolic and biological processes. On the contrary, its excess can be a serious health risk for chronically transfused patients, for example, thalassemia and sickle cell disease patients [1] [2]. End organ damage can result from deposition of excessive iron in organs such as hepatic parenchyma, endocrine organs, and cardiac cells [3] [4] [5]. "
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    ABSTRACT: MR has become a reliable and noninvasive method of hepatic iron quantification. Currently, most of the hepatic iron quantification is performed on 1.5 T MR, and the biopsy measurements have been paired with R 2 and R 2* values for 1.5 T MR. As the use of 3 T MR scanners is steadily increasing in clinical practice, it has become important to evaluate the practicality of calculating iron burden at 3 T MR. Hepatic iron quantification on 3 T MR requires a better understanding of the process and more stringent technical considerations. The purpose of this work is to focus on the technical challenges in establishing a relationship between T 2* values at 1.5 T MR and 3 T MR for hepatic iron concentration (HIC) and to develop an appropriately optimized MR protocol for the evaluation of T 2* values in the liver at 3 T magnetic field strength. We studied 22 sickle cell patients using multiecho fast gradient-echo sequence (MFGRE) 3 T MR and compared the results with serum ferritin and liver biopsy results. Our study showed that the quantification of hepatic iron on 3 T MRI in sickle cell disease patients correlates well with clinical blood test results and biopsy results. 3 T MR liver iron quantification based on MFGRE can be used for hepatic iron quantification in transfused patients.
    Full-text · Article · May 2013
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    • "Red blood cell transfusions have an important role in the treatment of acute and chronic complications of SCA by reducing the anemia, the concentration of Hb S and hemolysis(11). The clinical use of this treatment has often demonstrated a significant reduction in the incidence of acute chest syndrome, painful events, stroke and the number of hospital admissions(12,13). However, clinical and laboratory signs resulting from iron overload (IO) are observed after ten to twenty transfusions as there is no effective route of excreting iron from the organism(14). "
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    ABSTRACT: The aim of this study was to evaluate the impact of iron overload on the profile of interleukin-10 levels, biochemical parameters and oxidative stress in sickle cell anemia patients. A cross-sectional study was performed of 30 patients with molecular diagnosis of sickle cell anemia. Patients were stratified into two groups, according to the presence of iron overload: Iron overload (n = 15) and Non-iron overload (n = 15). Biochemical analyses were performed utilizing the Wiener CM 200 automatic analyzer. The interleukin-10 level was measured by capture ELISA using the BD OptEIAT commercial kit. Oxidative stress parameters were determined by spectrophotometry. Statistical analysis was performed using GraphPad Prism software (version 5.0) and statistical significance was established for p-values < 0.05 in all analyses. Biochemical analysis revealed significant elevations in the levels of uric acid, triglycerides, very low-density lipoprotein (VLDL), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine in the Iron overload Group compared to the Non-iron overload Group and significant decreases in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Ferritin levels correlated positively with uric acid concentrations (p-value < 0.05). The Iron overload Group showed lower interleukin-10 levels and catalase activity and higher nitrite and malondialdehyde levels compared with the Non-iron overload Group. The results of this study are important to develop further consistent studies that evaluate the effect of iron overload on the inflammatory profile and oxidative stress of patients with sickle cell anemia.
    Full-text · Article · Mar 2013 · Revista Brasileira de Hematologia e Hemoterapia
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    • "The number of lifetime transfusions has also been correlated with other markers of iron overload, such as non-transferrin-bound iron and serum ferritin levels (Inati et al, 2011). Furthermore, despite patients who are chronically transfused for longer periods being less likely to be hospitalized over a 12-month period, in those patients who were hospitalized, a positive correlation was observed between serum ferritin and hospitalization frequency (Fung et al, 2007). "
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    ABSTRACT: To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years.
    Full-text · Article · May 2011 · British Journal of Haematology
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