Response to hydroxycarbamide in pediatric β-thalassemia intermedia: 8 years’ follow-up in Egypt
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Hydroxycarbamide (hydroxyurea or HU) has been shown to increase fetal hemoglobin (HbF) in patients with β-thalassemia intermedia (TI). The reported effects of HU in increasing the total hemoglobin (Hb) have been inconsistent. Studies of long-term therapy with HU in pediatric TI are rather uncommon. A retrospective observational study was carried out to evaluate the clinical responses to HU in Egyptian patients with β-TI. One hundred patients; children (n = 82, mean age 9.9 ± 4.1 years) and adults (n = 18) were studied for the mean Hb, HbF%, median serum ferritin, transfusion history, and splenic size before and after HU therapy (mean dose 20.0 ± 4.2 mg/kg/day, range 10–29 mg/kg/day) over a follow-up period 4 to 96 months (mean 35.4 ± 19.2 months). Molecular studies were also done for group of patients (n = 42). The overall response rate to HU was 79 %; 46 % were minor responders (with a reduction in transfusion rate by 50 % or more and/or an increase in their total hemoglobin level by 1–2 g/dl) and 33 % major responders (becoming transfusion-free and/or having an increase in total hemoglobin level by >2 g/dl). Mean hemoglobin increased among responders from 6.9 ± 0.9 g/dl to 8.3 ± 1.4 g/dl (p < 0.001). A significant rise in mean HbF (27.0 vs. 42.5 %; p < 0.011) and a decrease in median serum ferritin (800 vs. 644 ng/ml; p < 0.001) were also observed among responders (n = 45). Transfusions stopped in 44 % of pretreatment frequently transfused responders (n = 11/25). Splenic size decreased in 37 % of patients (n = 30/81). The predominant β-thalassemia mutation was 1–6 (T > C) in 32/42 (76 %) of studied patients; 28/32 were responders. Bivariate analysis showed no predictors of response as regards sex, pediatric and adult age, splenic status, or genotype. Hydroxycarbamide is a good therapeutic modality in the management of pediatric as in adult TI patients. It can minimize the need for blood transfusion, concomitant iron overload, and blood-born viral transmission especially in developing countries like Egypt.
KeywordsHydroxycarbamide Hydroxyurea Thalassemia intermedia (TI) Children Egypt
Conflict of Interest
All authors have no conflict of interest that could inappropriately influence this work.
- 3.Najar R, Kaspar H, Shabaklo H, Makhoul N, Zalloua O (2004) Accurate and rapid prenatal diagnosis of the most frequent East Mediterranean β-thalassemia mutations. Am J Hematol 75(4):22–24Google Scholar
- 4.Thein SL (2005) Pathophysiology of ß-thalassemia—A guide to molecular therapies: Hematology; (1) 31Google Scholar
- 5.Higgs DR, Thein SL, Woods WG (2001) The molecular pathology of the thalassaemias. In: Weatherall DJ, Clegg B (eds) The thalassaemia syndromes, 4th edn. Blackwell Science, Oxford, England, pp 133–191Google Scholar
- 14.El-Gawhary S, El-Shafie S, Niazi M, Aziz M, El-Beshlawy A (2007) Study of beta-Thalassemia mutations using the polymerase chain reaction-amplification refractory mutation system and direct DNA sequencing techniques in a group of Egyptian Thalassemia patients. Hemoglobin 31(1):63–69CrossRefPubMedGoogle Scholar
- 25.Cang YC, Smith KD, Moore RD, Serjeant GR, Dover GJ (1995) An analysis of fetal haemoglobin variation in sickle cell disease: the relative contributions of the X-linked factor, b-globin haplotype, a-globin gene number, gender and age. Blood 85:1111–1117Google Scholar