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DOI: 10.1055/s-2005-836506
© Georg Thieme Verlag Stuttgart · New York
Intensification of Chelating-Therapy in Patients with Thalassemia major
Intensivierte Chelattherapie bei Patienten mit Thalassemia majorPublikationsverlauf
Publikationsdatum:
27. April 2005 (online)
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Abstract
With the introduction of “hypertransfusion” regimens the extent of disease- and therapy-related hemosiderosis has become the survival limiting factor for patients with β-thalassemia major as iron transferred with transfusions cannot be excreted by physiological means. Subsequent introduction of deferoxamine therapy for iron elimination and prophylaxis of hemosiderosis has improved prognosis and life quality of these patients considerably. We report our experience with seven adolescent patients with β-thalassemia and ineffective subcutaneous therapy and severe hemosiderosis-related organ complications. For that reason they received i. v. intensified chelate therapy. The patients were given 70 to 120 mg/kg DFO 7 days a week continuously via a Port-à-cath or Hickman central venous line. Under high-dose i. v. DFO therapy, serum ferritin levels significantly decreased in all patients. Target serum ferritin levels of 3 000 ng/ml were reached after 12 to 20 months of treatment. In 3 of the 5 patients that were treated for longer than 43 months serum ferritin levels even dropped below 2 000 ng/ml. Serum ferritin levels also correlated well with SQUID examinations. Therefore, monitoring of serum ferritin may be useful to monitor patient's compliance and control intensified DFO therapy. Continuous administration of the intensified DFO therapy induced normalization of liver function and left ventricular cardiac function in all patients who are still alive. Two patients died due to cardiac decompensation. In five patients 19 episodes of central catheter-related infections were observed (1.5 infections per 1 000 catheter days). No DFO-associated allergic reactions nor irreversible organ dysfunction were observed. Our results indicate that intensified i. v. DFO therapy is an effective and safe method for treatment of severe organ dysfunction in patients with thalassemia major. The most severe problems are catheter-related infections and inconsistent long-term compliance.
Zusammenfassung
Nach Einführung des Polytransfusionsregimes ist das Ausmaß der krankheits- und therapiebedingten Hämosiderose als lebenslimitierender Faktor für Patienten mit β-Thalassämia major zu sehen. Erst durch die Einführung der Deferroxamintherapie zur Eisenelimination und Hämosiderosenprophylaxe wurden die Prognose und Lebensqualität der Patienten deutlich verbessert. Wir berichten über unsere Erfahrungen bei 7 jugendlichen Patienten mit β-Thalassämie, die bei ineffektiver subkutaner Therapie und schweren hämosiderosebedingten Organkomplikationen eine intravenöse, intensivierte Chelattherapie erhielten. Die Patienten erhielten 70 -120 mg/kg KG Deferroxamin (DFO) an 7 Tagen pro Woche kontinuierlich über einen Port-à-cath- (5 ×) oder Hickman-Katheter (2 ×) infundiert. Ziel sollte ein Ferritinspiegel (FS) unter 3 000 ng/ml sein. Parallel zu dieser medizinischen Behandlung erfolgte eine psychologische Betreuung im Rahmen einer Patientengruppe. Unter hoch dosiertem DFO war bei allen Patienten der FS rückläufig (Ausgangswert im Median 8 820 ng/ml) und die Transaminasen normalisierten sich. Die intensivierte Chelattherapie wurde für 7-31 Monate durchgeführt. Die FS erreichten nach 12-20 Monaten 3 000 ng/ml. Erst nach mehr als 43 Monaten wurde bei 3 von 5 Patienten ein FS von kleiner 2 000 ng/ml erreicht. Bei regelmäßiger Durchführung der intensivierten DFO-Therapie konnte bei allen der noch lebenden Patienten eine Normalisierung der linksventrikulären Herzfunktion erreicht werden. 2 Patienten verstarben an einer kardialen Dekompensation. Bei 6 Patienten traten insgesamt 19 Episoden einer Katheterinfektion auf (1,5 Infektionen auf 1 000 Kathetertage). Wir beobachteten weder DFO-assoziierte allergische Reaktionen noch Organdysfunktionen. Unsere Ergebnisse lassen vermuten, dass die intensivierte DFO-Therapie eine effektive und sichere Methode zur Behandlung schwerster Organdysfunktionen bei Patienten mit Thalassämie major ist. Probleme sind in Katheterinfektionen und der wechselnden Langzeit-Compliance zu sehen.
Key words
Deferoxamin - SQUID - central venous line - Ferritin - cardial function
Schlüsselwörter
Deferoxamin - Ferritin - SQUID - Dauerverweilkatheter - Herzfunktion
References
- 1 Aldouri M A, Wonke B, Hoffbrand A V, Flynn D M, Ward S E, Agnew J E, Hilson A J. High incidence of cardiomyopathy in beta-thalassaemia patients receiving regular transfusion and iron chelation: reversal by intensified chelation. Acta Haematol. 1990; 84 113-117
- 2 Anderson L J, Westwood M A, Holden S, Davis B, Prescott E, Wonke B, Porter J B, Walker J M, Pennell D J. Myocardial iron clearance during reversal of siderotic cardiomyopathy with intravenous desferrioxamine: a prospective study using T2* cardiovascular magnetic resonance. Br J Haematol. 2004; 127 348-355
- 3 Beratis S. Noncompliance with iron chelation therapy in patients with beta thalassaemia. J Psychosom Res. 1989; 33 739-745
- 4 Brittenham G M, Griffith P M, Nienhuis A W, McLaren C E, Young N S, Tucker E E, Allen C J, Farrell D E, Harris J W. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med. 1994; 331 567-573
- 5 Cario H, Stahnke K, Sander S, Kohne E. Epidemiological situation and treatment of patients with thalassemia major in Germany: results of the German multicenter beta-thalassemia study. Ann Hematol. 2000; 79 7-12
- 6 Cazzola M, Borgna-Pignatti C, de Stefano P, Bergamaschi G, Bongo I G, Dezza L, Avato F. Internal distribution of excess iron and sources of serum ferritin in patients with thalassemia. Scand J Haematol. 1983; 30 289-296
- 7 Cohen A R, Mizanin J, Schwartz E. Rapid removal of excessive iron with daily, high-dose intravenous chelation therapy. J Pediatr. 1989; 115 151-155
- 8 Davis B A, Porter J B. Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk beta-thalassemia. Blood. 2000; 95 1229-1236
- 9 de Virgiliis S, Sanna G, Cornacchia G, Argiolu F, Murgia V, Porcu M, Cao A. Serum ferritin, liver iron stores, and liver histology in children with thalassaemia. Arch Dis Child. 1980; 55 43-45
- 10 Fosburg M T, Nathan D G. Treatment of Cooley's anemia. Blood. 1990; 76 435-444
- 11 Freedman M H, Grisaru D, Olivieri N, MacLusky I, Thorner P S. Pulmonary syndrome in patients with thalassemia major receiving intravenous deferoxamine infusions. Am J Dis Child. 1990; 144 565-569
- 12 Herold A, Rothe K, Woller T, Bierbach U, Bennek J. Early and late complications after implantation of central venous catheters. Klin Padiatr. 2003; 215 24-29
- 13 Hoch C, Gobel U, Janssen G. Psychosocial support of patients with homozygous beta-thalassaemia. Klin Padiatr. 2000; 212 216-219
- 14 Jensen P D, Jensen F T, Christensen T, Ellegaard J. Non-invasive assessment of tissue iron overload in the liver by magnetic resonance imaging. Br J Haematol. 1994; 87 171-184
- 15 Mitnick J S, Bosniak M A, Megibow A J, Karpatkin M, Feiner H D, Kutin N, Natta F Van, Piomelli S. CT in B-thalassemia: iron deposition in the liver, spleen, and lymph nodes. AJR Am J Roentgenol. 1981; 136 1191-1194
- 16 Nielsen P, Kordes U, Fischer R, Engelhardt R, Janka G E. SQUID-biosusceptometry in iron overloaded patients with hematologic diseases. Klin Padiatr. 2002; 214 218-222
- 17 Olivieri N F, Brittenham G M. Iron-chelating therapy and the treatment of thalassemia. Blood. 1997; 89 739-761
- 18 Olivieri N F, Nathan D G, MacMillan J H, Wayne A S, Liu P P, McGee A, Martin M, Koren G, Cohen A R. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med. 1994; 331 574-578
- 19 Pootrakul P, Josephson B, Huebers H A, Finch C A. Quantitation of ferritin iron in plasma, an explanation for non-transferrin iron. Blood. 1988; 71 1120-1123
- 20 Porter J B, Abeysinghe R D, Marshall L, Hider R C, Singh S. Kinetics of removal and reappearance of non-transferrin-bound plasma iron with deferoxamine therapy. Blood. 1996; 88 705-713
- 21 Wali Y A, Taqi A, Deghaidi A. Study of intermittent intravenous deferrioxamine high-dose therapy in heavily iron-loaded children with beta-thalassemia major poorly compliant to subcutaneous injections. Pediatr Hematol Oncol. 2004; 21 453-460
- 22 Wang W C, Ahmed N, Hanna M. Non-transferrin-bound iron in long-term transfusion in children with congenital anemias. J Pediatr. 1986; 108 552-557
- 23 Zurlo M G, De Stefano P, Borgna-Pignatti C, Di Palma A, Piga A, Melevendi C, Di Gregorio F, Burattini M G, Terzoli S. Survival and causes of death in thalassaemia major. Lancet. 1989; 2 27-30
Hans-Jürgen LawsM. D.
Department of Pediatric Oncology, Hematology and Immunology · Heinrich-Heine-University
Moorenstr. 5
40225 Düsseldorf
Germany
eMail: laws@uni-duesseldorf.de