Response to hydroxyurea in beta thalassemia major and intermedia: experience in western India

Clin Chim Acta. 2009 Sep;407(1-2):10-5. doi: 10.1016/j.cca.2009.06.019. Epub 2009 Jun 21.

Abstract

Background: The clinical and hematological response to hydroxyurea was evaluated in beta thalassemia patients in western India with variable clinical severity and correlated with genetic factors.

Materials and methods: Seventy-nine patients-[38-beta thalassemia intermedia-(group I), 41-beta thalassemia major-(group II)] on hydroxyurea therapy were followed-up for 20-24months.

Results: 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 gamma mRNA expression levels. Forty-one percent of patients in group I had associated alpha-thalassemia and 72.7% were XmnI (+/+). beta 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 beta 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 gamma mRNA expression levels. A significant decrease in serum ferritin was seen in both groups. 19% of patients could not tolerate the drug.

Conclusions: In group I, clinical response to hydroxyurea was better in patients with alpha-thalassemia, XmnI (+/+) and a higher mean fold increase in gamma mRNA expression. In group II, only one-third of patients showed a partial response.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Fetal Hemoglobin / metabolism
  • Gene Expression Regulation / drug effects
  • Haplotypes
  • Hematology
  • Humans
  • Hydroxyurea / pharmacology
  • Hydroxyurea / therapeutic use*
  • India
  • Male
  • Mutation
  • Polymorphism, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repetitive Sequences, Nucleic Acid
  • Treatment Outcome
  • Young Adult
  • beta-Thalassemia / blood
  • beta-Thalassemia / drug therapy*
  • beta-Thalassemia / genetics
  • beta-Thalassemia / pathology*

Substances

  • RNA, Messenger
  • Fetal Hemoglobin
  • Hydroxyurea