Drug Repurposing: Hydroxyurea Therapy Improves the Transfusion-Free Interval in HbE/Beta-Thalassemia—Major Patients with the Xmn I Polymorphism

Abstract

Aims:

HbE/β-thalassemia is the most prevalent form of severe β-thalassemia in Asian countries. Hydroxyurea (HU) is the most common drug used for the management of sickle-cell anemia but not thalassemia. In this study, we aimed to assess clinical HU response among the Bengali HbE/β-thalassemia patients with respect to the XmnI γ^Gglobin polymorphism and elucidate the association between this polymorphism and HU response efficacy.

Materials and Methods:

We enrolled 49 transfusion-dependent patients with HbE/β-thalassemia. Fetal hemoglobin levels were measured using high-performance liquid chromatography and complete blood counts were determined pre- and post-HU therapy. Polymerase chain reaction-restriction fragment length polymorphism analyses were performed for genotyping the XmnI γ^Gglobin polymorphism.

Results:

A total of 30 (61.22%) patients were found to be responders, whereas the remaining 19 (38.78%) were nonresponders. We found 33 patients with the heterozygous (C/T) and three with the homozygous mutant (T/T) genotype status. We obtained a statistically significant correlation (p < 0.001) between the XmnI polymorphism genotype and transfusion-free interval. Patients with the XmnI polymorphism were found to be good responders for HU therapy and showed increased hemoglobin levels.

Conclusions:

Our findings indicate that HU is a potential drug candidate for thalassemia management, particularly for HbE/β-thalassemia. These results hold implications in repurposing HU as an effective and efficient therapy for HbE/β-thalassemia.