Hydroxyurea in the treatment of major ?-thalassemia and importance of genetic screening
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- 作者：M. Alebouyeh ; F. Moussavi ; H. Haddad-Deylami and P. Vossough
- 关键词：Major ; thalassemia ; Genetic screening ; IVSII ; 1 mutation ; Xmn1 polymorphism ; Hydroxyurea
- 刊名：Annals of Hematology
- 出版年：2004
- 出版时间：July 2004
- 年：2004
- 卷：83
- 期：7
- 页码：430-433
- 全文大小：124 KB
- 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Hematology
Oncology - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-0584
文摘
Efforts have been undertaken to find an alternative approach to packed red cell transfusion (PRCT) in major -thalassemia. Augmentation of fetal hemoglobin (HbF) by hydroxyurea (HU) has been reported to be less effective in this condition as compared to sickle cell anemia due to molecular heterogeneity of the former disease. HU efficacy and its relation to Xmn1 polymorphism and IVSII-1 mutation was evaluated in major -thalassemics. Forty-five patients, M/F ratio 0.8, aged 6–33 years, received oral HU, 20 mg/kg per day, 4 days per week and daily1 mg folic acid. Thirty-six patients were PRCT dependent (group A) and nine independent (group B). The aim was to stabilize or increase pre-PRCT Hb over 10.0±0.5 g/dl and to reduce the need or cease the PRCT in group A and to increase Hb level and curb the ineffective erythropoesis, e.g., splenomegaly, facial bone deformity, in group B. HU was administered for at least 6 months (mean: 9 months) and discontinued in case of response failure. Screening for Xmn1 polymorphism and IVSII-1 mutation was carried out in most patients. In group A, 25 patients have become PRCT independent for a period of 2.5–7.3 years (mean: 4 years). The mean Hb, pre-HU 10.0 and post-HU 10.7 g/dl (range: 8.8–13.7 g/dl), mean serum ferritin pre- and post-HU was1877 and 525 ng/ml. The PRCT requirement was reduced in one patient, and ten patients did not respond. In group B HU has been given over 3.3 years (range: 2.8–4.8 years), Hb increased from 9.3 to 10.4/dl, and there was no tangible progression of ineffective erythropoesis. Responders in both groups expressed more comfort with this regimen. Xmn1 and IVSII-1 (homo- and/or heterozygosis) are relevant markers in most responding patients. Molecular determination of genetic markers in early childhood will help to identify candidates for pharmacological HbF switching by HU.