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Previous Volume 331:567-573 September 1, 1994 Number 9 Next

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ABSTRACT

Background To determine whether deferoxamine prevents the complications of transfusional iron overload in thalassemia major, we evaluated 59 patients (30 were female and 29 male; age range, 7 to 31 years) periodically for 4 to 10 years or until death.

Methods At each follow-up visit, we performed a detailed clinical and laboratory evaluation and measured hepatic iron stores with a noninvasive magnetic device.

Results The body iron burden as assessed by magnetic measurement of hepatic iron stores was closely correlated (R = 0.89, P<0.001) with the ratio of cumulative transfusional iron load to cumulative deferoxamine use (expressed in millimoles of iron per kilogram of body weight, in relation to grams of deferoxamine per kilogram, transformed into the natural logarithm). Each increase of one unit in the natural logarithm of the ratio (transfusional iron load to deferoxamine use) was associated with an increased risk of impaired glucose tolerance (relative risk, 19.3; 95 percent confidence interval, 4.8 to 77.4), diabetes mellitus (relative risk, 9.2; 95 percent confidence interval, 1.8 to 47.7), cardiac disease (relative risk, 9.9; 95 percent confidence interval, 1.9 to 51.2), and death (relative risk, 12.6; 95 percent confidence interval, 2.4 to 65.4). All nine deaths during the study occurred among the 23 patients who had begun chelation therapy later and used less deferoxamine in relation to their transfusional iron load (P<0.001).

Conclusions The early use of deferoxamine in an amount proportional to the transfusional iron load reduces the body iron burden and helps protect against diabetes mellitus, cardiac disease, and early death in patients with thalassemia major.

Source Information

From the Departments of Medicine (G.M.B., J.W.H.) and Physics (C.J.A., D.E.F.), Case Western Reserve University, Cleveland; the Department of Mathematics, Moorhead State University, Moorhead, Minn. (C.E.M.); St. Jude Children's Research Hospital, Memphis, Tenn. (A.W.N.); and the Clinical Hematology Branch (P.M.G., N.S.Y.) and Cardiology Branch (E.E.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.

Address reprint requests to Dr. Brittenham at MetroHealth Medical Center, 3395 Scranton Rd., Cleveland, OH 44109.

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Deferoxamine in Thalassemia Major
Splendiani G., Tozzo C., Mazzarella V., Casciani C. U., Lucarelli G., Clift R., Angelucci E., Cazzola M., Locatelli F., De Stefano P., Olivieri N. F., Nathan D. G., Cohen A. R.
Extract | Full Text  
N Engl J Med 1995; 332:270-273, Jan 26, 1995. Correspondence

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• Jensen, P. D., Jensen, F. T., Christensen, T., Eiskjaer, H., Baandrup, U., Nielsen, J. L. (2003). Evaluation of myocardial iron by magnetic resonance imaging during iron chelation therapy with deferrioxamine: indication of close relation between myocardial iron content and chelatable iron pool. Blood 101: 4632-4639 [Abstract] [Full Text]  
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• Schwartz, K. A., Li, Z., Schwartz, D. E., Cooper, T. G., Braselton, W. E. (2002). Earliest cardiac toxicity induced by iron overload selectively inhibits electrical conduction. J. Appl. Physiol. 93: 746-751 [Abstract] [Full Text]  
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• Davis, B. A., Porter, J. B. (2000). Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk beta -thalassemia. Blood 95: 1229-1236 [Abstract] [Full Text]  
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• Kuryshev, Y. A., Brittenham, G. M., Fujioka, H., Kannan, P., Shieh, C.-C., Cohen, S. A., Brown, A. M. (1999). Decreased Sodium and Increased Transient Outward Potassium Currents in Iron-Loaded Cardiac Myocytes : Implications for the Arrhythmogenesis of Human Siderotic Heart Disease. Circulation 100: 675-683 [Abstract] [Full Text]  
• Olivieri, N. F. (1999). The {beta}-Thalassemias. NEJM 341: 99-109 [Full Text]  
• Tsushima, R. G., Wickenden, A. D., Bouchard, R. A., Oudit, G. Y., Liu, P. P., Backx, P. H. (1999). Modulation of Iron Uptake in Heart by L-Type Ca2+ Channel Modifiers : Possible Implications in Iron Overload. Circ. Res. 84: 1302-1309 [Abstract] [Full Text]  
• Horwitz, L. D, Rosenthal, E. A (1999). Iron-mediated cardiovascular injury. Vasc Med 4: 93-99 [Abstract]  
• Bergeron, R. J., Wiegand, J., Brittenham, G. M. (1999). HBED: The Continuing Development of a Potential Alternative to Deferoxamine for Iron-Chelating Therapy. Blood 93: 370-375 [Abstract] [Full Text]  
• Tricta, F., Spino, M., Callea, F., Nathan, D. G., Weatherall, D. J., Stella, M., Pinzello, G., Maggio, A., Wonke, B., Telfer, P., Hoffbrand, A.V., Grady, R. W., Giardina, P. J., Cohen, A. R., Martin, M. B., Brittenham, G. M., Fleming, K. A., Templeton, D. M., Olivieri, N. F., Kowdley, K. V., Kaplan, M. M. (1998). Iron Chelation with Oral Deferiprone in Patients with Thalassemia. NEJM 339: 1710-1714 [Full Text]  
• Economou-Petersen, E., Aessopos, A., Kladi, A., Flevari, P., Karabatsos, F., Fragodimitri, C., Nicolaidis, P., Vrettou, H., Vassilopoulos, D., Karagiorga-Lagana, M., Kremastinos, D. Th., Petersen, M. B. (1998). Apolipoprotein E &b.epsi;4 Allele as a Genetic Risk Factor for Left Ventricular Failure in Homozygous beta -Thalassemia. Blood 92: 3455-3459 [Abstract] [Full Text]  
• Olivieri, N. F., Brittenham, G. M., McLaren, C. E., Templeton, D. M., Cameron, R. G., McClelland, R. A., Burt, A. D., Fleming, K. A. (1998). Long-Term Safety and Effectiveness of Iron-Chelation Therapy with Deferiprone for Thalassemia Major. NEJM 339: 417-423 [Abstract] [Full Text]  
• Kowdley, K. V., Kaplan, M. M. (1998). Iron-Chelation Therapy with Oral Deferiprone -- Toxicity or Lack of Efficacy?. NEJM 339: 468-469 [Full Text]  
• BERGERON, R. J., WIEGAND, J., RATLIFF-THOMPSON, K., WEIMAR, W. R. (1998). The Origin of the Differences in (R)- and (S)-Desmethyldesferrithiocin: Iron-Clearing Properties. Ann. N. Y. Acad. Sci. 850: 202-216 [Abstract] [Full Text]  
• OLIVIERI, N. F., BRITTENHAM, G. M. (1998). Long-Term Trials of Deferiprone in Cooley's Anemia. Ann. N. Y. Acad. Sci. 850: 217-222 [Abstract] [Full Text]  
• BORGNA-PIGNATTI, C., RUGOLOTTO, S., DE STEFANO, P., PIGA, A., DI GREGORIO, F., GAMBERINI, M. R., SABATO, V., MELEVENDI, C., CAPPELLINI, M. D., VERLATO, G. (1998). Survival and Disease Complications in Thalassemia Major. Ann. N. Y. Acad. Sci. 850: 227-231 [Abstract] [Full Text]  
• JESSUP, M., MANNO, C. S. (1998). Diagnosis and Management of Iron-induced Heart Disease in Cooley's Anemia. Ann. N. Y. Acad. Sci. 850: 242-250 [Abstract] [Full Text]  
• PIGA, A., LONGO, F., VOI, V., FACELLO, S., MINIERO, R., DRESOW, B. (1998). Late Effects of Bone Marrow Transplantation for Thalassemia. Ann. N. Y. Acad. Sci. 850: 294-299 [Abstract] [Full Text]  
• ROSE, C., CAMBIE, C., FORZY, G., MAHIEU, M., FENAUX, P., BAUTERS, F. (1998). Deferoxamine Stability in Intravenous Solution. Ann. N. Y. Acad. Sci. 850: 488-489 [Full Text]  
• Chui, D. H.K., Waye, J. S. (1998). Hydrops Fetalis Caused by alpha -Thalassemia: An Emerging Health Care Problem. Blood 91: 2213-2222 [Full Text]  
• Bergeron, R. J., Wiegand, J., Brittenham, G. M. (1998). HBED: A Potential Alternative to Deferoxamine for Iron-Chelating Therapy. Blood 91: 1446-1452 [Abstract] [Full Text]  
• Hoffbrand, A. V., AL-Refaie, F., Davis, B., Siritanakatkul, N., Jackson, B. F.A., Cochrane, J., Prescott, E., Wonke, B. (1998). Long-Term Trial of Deferiprone in 51 Transfusion-Dependent Iron Overloaded Patients. Blood 91: 295-300 [Abstract] [Full Text]  
• Angelucci, E., Giovagnoni, A., Valeri, G., Paci, E., Ripalti, M., Muretto, P., McLaren, C., Brittenham, G. M., Lucarelli, G. (1997). Limitations of Magnetic Resonance Imaging in Measurement of Hepatic Iron. Blood 90: 4736-4742 [Abstract] [Full Text]  
• Di Marco, V., Iacono, O. L., Almasio, P., Ciaccio, C., Capra, M., Rizzo, M., Malizia, R., Maggio, A., Fabiano, C., Barbaria, F., Craxi, A. (1997). Long-Term Efficacy of alpha -Interferon in beta -Thalassemics With Chronic Hepatitis C. Blood 90: 2207-2212 [Abstract] [Full Text]  
• Weatherall, D J (1997). Fortnightly review: The thalassaemias. BMJ 314: 1675-1675 [Full Text]  
• Lau, Y.-L., Chan, L.-C., Chan, Y.-Y. A., Ha, S.-Y., Yeung, C.-Y., Waye, J. S., Chui, D. H.K. (1997). Prevalence and Genotypes of {alpha}- and {beta}-Thalassemia Carriers in Hong Kong -- Implications for Population Screening. NEJM 336: 1298-1301 [Abstract] [Full Text]  
• Olivieri, N. F., Brittenham, G. M. (1997). Iron-Chelating Therapy and the Treatment of Thalassemia. Blood 89: 739-761 [Full Text]  
• Olivieri, N. F., Brittenham, G. M., Matsui, D., Berkovitch, M., Blendis, L. M., Cameron, R. G., McClelland, R. A., Liu, P. P., Templeton, D. M., Koren, G. (1995). Iron-Chelation Therapy with Oral Deferiprone in Patients with Thalassemia Major. NEJM 332: 918-922 [Abstract] [Full Text]  
• Splendiani, G., Tozzo, C., Mazzarella, V., Casciani, C. U., Lucarelli, G., Clift, R., Angelucci, E., Cazzola, M., Locatelli, F., De Stefano, P., Olivieri, N. F., Nathan, D. G., Cohen, A. R. (1995). Deferoxamine in Thalassemia Major. NEJM 332: 270-273 [Full Text]  
• (1994). DEFEROXAMINE FOR THALASSEMIA MAJOR. JWatch General 1994: 3-3 [Full Text]  
• Dover, G. J., Valle, D. (1994). Therapy for {beta}-Thalassemia -- A Paradigm for the Treatment of Genetic Disorders. NEJM 331: 609-610 [Full Text]