Response to hydroxyurea in β thalassemia major and intermedia: Experience in western India

• Published in: Clinica chimica acta 2009-09, Vol.407 (1), p.10-15
• Main Authors: Italia, Khushnooma Y., Jijina, Farah J., Merchant, Rashid, Panjwani, Sangeeta, Nadkarni, Anita H., Sawant, Pratibha M., Nair, Sona B., Ghosh, Kanjaksha, Colah, Roshan B.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; beta-Thalassemia - blood; beta-Thalassemia - drug therapy; beta-Thalassemia - genetics; beta-Thalassemia - pathology; Child; Child, Preschool; Female; Fetal Hemoglobin - metabolism; Gene Expression Regulation - drug effects; Haplotypes; Hematology; Humans; Hydroxyurea; Hydroxyurea - pharmacology; Hydroxyurea - therapeutic use; India; Male; Mutation; Polymorphism, Genetic; Repetitive Sequences, Nucleic Acid; RNA, Messenger - genetics; RNA, Messenger - metabolism; Treatment Outcome; XmnI polymorphism; Young Adult; α–thalassemia; β thalassemia; γ mRNA expression
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2009.06.019

The clinical and hematological response to hydroxyurea was evaluated in β thalassemia patients in western India with variable clinical severity and correlated with genetic factors. Seventy-nine patients-[38-β thalassemia intermedia-(group I), 41-β thalassemia major-(group II)] on hydroxyurea therapy were followed-up for 20–24 months. Among the frequently transfused patients in group I, 58% became transfusion independent and 16% showed a 50% reduction in transfusions after therapy which correlated with a higher mean fold increase in HbF and γ mRNA expression levels. Forty-one percent of patients in group I had associated α-thalassemia and 72.7% were XmnI (+/+). β thalassemia chromosomes among the responders of group I (41%) were linked to haplotype (− + + − + + − − +) as against haplotype (+ − − − − − − − +) being more common among the non-responders. Response was not linked to the β thalassemia mutations. Thirty-two percent of group II patients showed a 50% reduction in their transfusion requirements after therapy which also correlated with a higher mean fold increase in HbF and γ mRNA expression levels. A significant decrease in serum ferritin was seen in both groups. 19% of patients could not tolerate the drug. In group I, clinical response to hydroxyurea was better in patients with α–thalassemia, XmnI (+/+) and a higher mean fold increase in γ mRNA expression. In group II, only one-third of patients showed a partial response.