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

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.

• Authors: Khushnooma Y Italia, Farah J Jijina, Rashid Merchant, Sangeeta Panjwani, Anita H Nadkarni, Pratibha M Sawant, Sona B Nair, Kanjaksha Ghosh, Roshan B Colah
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 407 Issue 1-2 Pg. 10-5 (Sep 2009) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 19545554 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Fetal Hemoglobin
• Hydroxyurea

Topics

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