EFFICACY AND ADVERSE EFFECTS OF ORAL IRON CHELATOR DEFERIPRONE (L1, 1,2- DIMETHYL-3-HYDROXYPYRID-4-ONE) IN PATIENTS WITH BETA THALASSAEMIA MAJOR IN PAKISTAN
Abstract
Background: Deferiprone (DFP,L1) is a bidentate oral iron chelator which binds to iron in a3:1 ratio. It has the potential advantage of reduced cost and increased compliance. Weconducted a study in order to determine the efficacy and adverse effects of DFP in Pakistanithalassaemic patients. Methods: A group of 26 thalassaemic patients entered the studyduring the period Jan 1999 to Aug 2002. DFP supplied by Lipomed, Switzerland was givenat a daily dose of 75 mg/kg/day (range 50-75 mg/kg/day). After giving informed writtenconsent all the patients were subjected to clinical examination and investigations formonitoring the response. Blood complete picture, liver function tests, blood urea &creatinine, antinuclear factor antibodies (ANF) were tested in all cases before starting DFPtreatment. Results: The patients ages ranged from 11 to 27 years, 16 were male and 10 werefemale. Initial serum ferritin level ranged from 3100-8800 μg/l, mean serum ferritin levelwas 7129±1467 μg/l (95% CI 6536 – 7721 μg/l). ECG and Echocardiography wasperformed in all cases and in 11 cases Cardiac Multigated acquisition (MUGA) Scan wasalso performed and six patients with impaired left ventricular function were identified. Fourpatients were lost to follow up and one patient died due to cardiomyopathy. Among theremaining 21 patients serum ferritin levels dropped to 1900μg/l to 5600μg/l with mean levelof 4288 μg/l (95%CI 3874 – 4702 μg/l), SD 911 μg/l. Significance of difference was (p <0.001) by Paired samples ‘t’ test. Six patients had gastrointestinal symptoms along with twohaving arthropathy. ANF positivity was not detected in any patient while on DFP treatment.Similarly, agranulocytosis was not detected in any patient. Conclusion. Mean serum ferritinlevel estimated at the start of trial was 7129 μg/l. This shows that Pakistani thalassaemicpatients are quite iron overloaded due to socioeconomic reasons that are peculiar to oursetup. In this study DFP was well tolerated and caused fewer side effects. It had much betterpatient compliance and was effective in lowering serum ferritin level in previously mostpoorly chelated patients.Keywords: Thalassaemia, Deferiprone, Transfusion iron overload, Cardiomyopathy,DemographyReferences
Ahmed S, Saleem M, Modell B, Petrou M. Screening
extended families for genetic hemoglobin disorders in
Pakistan. N Engl J Med 2002;347:1162-8.
Ahmed S, Petrou M, Saleem M. Molecular genetics of
beta-thalassaemia in Pakistan: a basis for prenatal
diagnosis. Br J Haematol 1996 Sep;94(3):476-82.
Khattak MF, Saleem M. Prevalence of heterozygous
beta thalassaemia in northern areas of Pakistan. J Pak
Med Assoc 1992; 42:32-4.
Alwan A, Modell B. Recommendations for introducing
genetics services in developing countries. Nat Rev
Genet 2003; 4: 61-8.
Al-Refaie FN, De Silva CE, Wonke B, Hoffbrand AV.
Changes in transferrin saturation after treatment with the
oral iron chelator deferiprone in patient with iron
overload. J Clin Pathol; 1995; 48: 110-4.
Al-Rafaie FN, Sheppard LN, Nortey P, Wonke B,
Hoffbrand AV. Pharmacokinetics of the oral iron
chelator deferiprone (L1) in patients with iron overload.
Br J Haematol 1995; 89: 403-8.
Kontoghiorghes GJ, Bartlett AN, Hoffbrand AV,
Golddard JG, Shepard L, Barr J, et al. Long term trail
with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-
-one (L1). Iron chelation and metabolic studies. Br J
Haematol 1990; 76;295-300.
Porter JB. Practical management of iron overload. Br J
Haematol; 2001; 115:239-52.
Wood JC, Tyszka JM, Carson S, Nelson MD, Coates
TD. Myocardial iron loading in transfusion dependent
thalassemia and sickle cell disease. Blood. 2004;
:1934-1936.
Hoffbrand AV, Cohen A, Hershko C. Role of
deferiprone in chelation therapy for transfusional iron
overload. Blood 2003;102: 17-24.
Bhatti FA, Amin M, Saleem M. Prevalence of antibody
to hepatitis C virus in Pakistani thalassaemics by particle
agglutination test utilizing C-200 and C22-3 viral
antigen coated practical. J Pak Med Assoc 1995; 45
(10): 269-71.
Bergeron RJ, Streiff RR, Weigand J, Luchetta G, Creary
EA, Peter HH. A comparison of the iron chelating
properties of 1,2-dimethyl-3-hydroxypyrid-4-one, 1,2-
diethyl-3-hydroxypyrid-4-one and deferoxamine. Blood
; 79: 1882-90.
Liu ZD, Liu DY, Lu SL, Hider R. Synthesis,
physicochemical properties and biological evaluation of
aromatic ester prodrugs of 1-(2’-hydroxyethyl)-2-ethyl-
-hydroxypyridin-4-one (CP102): orally active iron
chelators with clinical potential. J Pharm Pharmacol
; 51:555-64.
Al-Refaie FN, Hershko C, Hoffbrand AV, Kosaryan M,
Olivieri, NF, Tondury P, et al. Results of long term
deferiprone (L1) therapy: a report by the International
Study Group on Oral Iron Chelators. Br J Haematol
; 91: 224-9.
Modell B, Khan M, Darlison M. Survival in betathalassaemia major in the UK: data from the UK
Thalassaemia Register. Lancet 2000;355:2051-2.
Agarwal MB, Gupte, SS, Viswanathan C, Vasandani D,
Ramanathan J, Desal N. Long-term assessment of
efficacy and safety of L1, an oral iron chelator, in
transfusion dependent thalassaemia: Indian trail. Br J
Haematol 1992; 82: 460-6.
Refaie FN, Wonke B, Hoffbrand AV, Wickens, DG,
Nortey P, Kontoghiorghes GJ. Efficacy and possible
adverse effects of the oral iron chelator 1,2 dimethyl-3-
hydroxypyrid-4 one (L1) in thalassemia major. Blood
; 80: 593-9.
Olivieri NF, Koren G, Hermann C, Bentur Y, Chung D,
Klein J, et al. Comparison of oral iron chelator L1 and
desferrioxamine in iron loaded patients. Lancet 1990;
-9.
Stella M, Pinzello G, Maggio A. Iron chelation with oral
deferiprone in patients with thalassaemia. New Eng J
Med 1998; 339: 172-4.
Piga A, Gaglioti C, Fogliacco E, Tricta F. Comparative
effects of deferiprone and deferoxamine on survival and
cardiac disease in patients with thalassemia major: a
retrospective analysis. Haematologica 2003;88: 489-96.
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