WHAT A HİGH FREQUENCY OF DEFERİPRONE-İNDUCED AGRANULOCYTOSİS İN A TURKİSH POPULATİON OF THALASSEMİA MAJOR

Yıl 2011, Cilt: 2 Sayı: 8, 17 - 27, 03.03.2015

Mehmet Helvacı Süleyman Oktar Figen Günay Müge Tellioğlu Vefik Arıca Hasan Kaya

Öz

Background: Deferiprone may cause agranulocytosis.
Methods: All cases of thalassemia major followed by Center of Hereditary Blood Disorders
of the Iskenderun Public Hospital and Hematology Department of the Mustafa Kemal
University were retrospectively reviewed.
Results: Eighteen cases were on desferrioxamine therapy, five on deferiprone, and 21 on both
initially. Three of 26 deferiprone receiving cases developed agranulocytosis in the first year of
therapy, so its frequency was 11.5%. When we compared the ratio with previous reports (0.5-
1%), difference was significant (p<0.01). Milder neutropenia was observed in none of
deferiprone receiving cases, which was significantly lower (0.0% vs 8.5%, p<0.01). Three
agranulocytosis cases were both on desferrioxamine and deferiprone therapies, and only one
case was female. Additionally, two of them were splenectomized, and none was antiHCV
positive.
Conclusion: Hereditary factors and combination with desferrioxamine are probably the
most important factors for higher frequency of deferiprone induced agranulocytosis rather
than female sex, splenectomy operations, or hepatitis infections.  

Anahtar Kelimeler

Thalassemia major, iron overload, desferrioxamine, deferiprone, ICL 670

Bir Türk talasemi majör hasta grubunda deferiprona bağlı agranülositozun yüksek sıklığı

Öz

Deferipronun agranülositoz yapma potansiyeli mevcuttur. İskenderun Devlet Hastanesi Kalıtsal Kan Hastalıkları Merkezi ve Mustafa Kemal Üniversitesi Tıp Fakültesi Hematoloji Servisince takip edilen talasemi majör hastalarının kayıtları incelendi. Onsekiz vaka desferoksamin, beş vaka deferipron ve 21 vaka her ikisini de kullanmaktaydı. Tedavinin ilk yılında deferipron kullanan 26 hastadan üçünde (%11.5) agranülositoz gelişti. Bu oran, önceki yayınlarda belirtilen agranülositoz görülme oranı olan %0.5-1 ile karşılaştırıldığında, arada istatistiksel olarak anlamlı bir farkın mevcut olduğu görüldü (p<0.01). Hafif nötropeni hiçbir vakada görülmedi ve bu oran da anlamlı şekilde düşüktü (%0.0’a karşılık %8.5, p<0.01). Agranülositoz görülen vakaların üçü hem desferoksamin hem de deferipron kullanmaktaydı ve vakaların bir tanesi bayandı. Ayrıca, agranülositoz görülen vakaların ikisi splenektomiliydi ve hiçbir vakada antiHCV pozitifliği tespit edilmedi. Sonuç olarak, kalıtımsal faktörler ve desferoksamin ile birlikte kullanımın, deferiprona bağlı agranülositoz için önemli risk faktörleri olduğu ve bayan cinsiyet, geçirilmiş splenektomi veya hepatit enfeksiyonlarının getirdiği risklerin düşük olabileceği düşünüldü.

Anahtar Kelimeler

Talasemi majör, artmış demir yükü, desferoksamin, deferipron, ICL

Kaynakça

• 1. Capellini N, Cohen A, Eleftheriou A, Piga A, Porter J, eds. Guidelines for Clinical Management of Thalassemia. Nicosia, Cyprus: Thalassemia International Federation; 2000.
• 2. Angelucci E, Muretto P, Nicolucci A, Baronciani D, Erer B, Gaziev J, et al. Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation. Blood 2002; 100: 17- 21.
• 3. Borgna-Pignatti C, Cohen A. Evaluation of a new method of administration of the iron chelating agent deferoxamine. J Pediatr 1997; 130: 86-88.
• 4. Araujo A, Kosaryan M, MacDowell A, Wickens D, Puri S, Wanke B, et al. A novel delivery system for continuous desferrioxamine infusion in transfusional iron overload. Br J Haematol 1996; 93: 835-837.
• 5. Davis BA, Porter JB. Long-term outcome of continuous 24-hour deferoxamine infusions via indwelling intravenous catheters in high-risk beta-thalassemia. Blood 2000; 95: 1229-1236.
• 6. Al-Refaie FN, Sheppard LN, Nortey P, Wonke B, Hoffbrand AV. Pharmacokinetics of the oral chelator deferiprone (L1) in patients with iron overload. Br J Haematol 1995; 89: 403–408
• 7. Shalev O, Repka T, Goldfarb A, Grienberg L, Abrahamov A, Olivieri NF, et al. Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassaemic and sickle red blood cells both in vitro and in vivo. Blood 1995; 86: 2008-2013.
• 8. Pootrakul P, Sirankapracha P, Sankote J, Kachintom U, Maungsub W, Sriphen K, et al. Clinical trial of deferiprone iron chelation therapy in betathalassaemia/haemoglobin E patients in Thailand. Br J Haematol 2003; 122: 305-310.
• 9. Wonke B, Wright C, Hoffbrand AV. Combined therapy with deferiprone and desferrioxamine. Br J Haematol 1998; 103: 361-364.
• 10. Origa R, Bina P, Agus A, Crobu G, Defraia E, Dessi C, et al. Combined therapy with deferiprone and desferrioxamine in thalassemia major. Haematologica 2005; 90: 1309- 1314. 11. Cohen AR, Galanello R, Piga A, Sanctis VD, Tricta F. Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. Blood 2003; 102: 1583- 1587.
• 12. Beutler E, Hoffbrand AV, Cook JD. Iron Deficiency and Overload. Hematology Am Soc Hematol Educ Program 2003: 40-61.
• 13. Olivieri NF, Brittenham GM, Matsui D, Berkovitch M, Blendis LM, Cameron RG, et al. Iron-chelation therapy with oral deferiprone in patients with thalassemia major. N Engl J Med 1995; 332: 918-922.
• 14. Wonke B, Prescott E, Westwood M, Anderson L, Pennell D. Effects of combination treatment deferiprone and desferrioxamine to clear iron from the heart. The 9th International Conference on Thalassemia and Hemoglobinopathies; Palermo 15-19 October 2003.
• 15. Cohen AR, Galanella R, Piga A, DiPalma A, Vullo C, Tricta F. Safety profile of the oral iron chelator deferiprone: a multicenter study. Br J Haematol 2000; 108: 305-312.
• 16. Ceci A, Baiardi P, Felisi M, Cappellini MD, Carnelli V, De Sanctis V, et al. The safety and effectiveness of deferiprone in a large-scale, 3-year study in Italian patients. Br J Haematol 2002; 118: 330-336.
• 17. Olivieri NF, Brittenham GM, McLaren CE, Templeton DM, Cameron RG, McClelland RA, et al. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. N Engl J Med 1998; 339: 417-423
• 18. Arboretti R, Tognoni G, Alberti D. Pharmacosurveillance and quality of care of thalassaemic patients. Eur J Clin Pharmacol 2001; 56: 915-922.
• 19. Cohen A, Galanello R, Piga A, Vullo C, Tricta F. A multi-center safety trial of the oral iron chelator deferiprone. Ann N Y Acad Sci 1998; 850: 223-226.
• 20. Agarwal MB, Gupta SS, Vismanathan C, Vasandani D, Ramanathan J, Desai N, et al: Long-term assessment of efficacy and safety of L1, an oral iron chelator, in transfusion dependent thalassaemia: Indian trial. Br J Haematol 1992; 82: 460.
• 21. Hoffbrand AV. Oral iron chelation. Semin Hematol 1996; 33: 1. 22. Gerson SL, Meltzer H. Mechanisms of clozapine-induced agranulocytosis. Drug Safety 1992; 7: 17-25.
• 23. Hoffbrand AV, AL-Refaie FN, Davis B, Siritanakatkul N, Jackson BFA, Cochrane J, et al. Long-Term Trial of Deferiprone in 51 Transfusion-Dependent Iron Overloaded Patients. Blood 1998; 91: 295-300.
• 24. Cunningham JM, Hunter AB, Hoffbrand AV, Al-Refaie FN, Veys P, Wilkes S, et al. Differential toxicity of -ketohydroxypyridine iron chelators and desferrioxamine to human hemopoietic precursors in vitro. Eur J Haematol 1994; 52: 176.