Hydroxyurea Treatment in Transfusion-Dependent β-Thalassemia Patients

Abstract

Background:β-Thalassemia is an inherited hemoglobin disorder caused by defective synthesis of ß-globin chains. Hemoglobin (Hb) F induction is a possible therapeutic approach which can partially compensate for α and non-α globin chains imbalance.Objectives:We aimed to investigate the efficacy and safety of Hydroxyurea (HU) in diminishing transfusion requirements of patients with β-thalassemia major in Southern Iran.Patients and Methods:In this single-arm clinical trial, all transfusion-dependent β-thalassemia patients older than two years old (n = 97) who had inclusion criteria of the study and had been registered for at least six months in Dastgheib thalassemia outpatient clinic (a referral center affiliated to Shiraz University of Medical Sciences) were evaluated from October 2010 to December 2011. The patients were treated with HU with a mean dose of 10.5 mg/kg for a mean duration of 8 months (range 3-14 months). Transfusion needs and Hb levels were compared before and after HU treatment.Results:The mean volume of blood transfusion decreased significantly following HU treatment (0.71 mL/kg/day vs. 0.43 mL/kg/day, P < 0.001). Two-thirds of the patients showed good and partial response. No serious adverse reaction was observed except persistent neutropenia in two patients.Conclusions:Hydroxyurea can be safely used in some transfusion-dependent β-thalassemia patients to decrease their transfusion needs.

Efficacy and safety of high dose hydroxyurea in transfusion dependent thalassemic children: a quasi experimental study

“…Similar to that our study, post-HU HbF level was significantly higher in good responders compared with partial and non-responders (p< 0.001), also in partial responders, a significant higher level of post-HU HbF was observed compared with non-responders (p=0.036) in study done by Mohammad Reza Bordbar et al 15 In 0 responders out of 45 patients. 13,14,[16][17][18] This difference is supposed to be due to the interaction of many factors, including different genetic mutations, α and γ globin chains production, XmnI polymorphism and other biochemical factors contribute to the therapeutic response to HU.…”

Complementary and alternative medicine use in thalassemia patients in Shiraz, southern Iran: A cross-sectional study

“…Fetal hemoglobin induction by drugs such as hydroxyurea, butyrates, mithramycin, andrapamycin was found to have some effects in decreasing the transfusion requirements of some thalassemia patients especially those with thalassemia intermedia. 11 , 12 , 13 Despite acceptable efficacy and safety especially with hydroxyurea, some scientists are still concerned with the long-standing carcinogenicity of these drugs. Introduction of novel hemoglobin F inducers like simvastatin and some herbal products such as Wheatgrass, Piceatannol, and Resveratrol has brought some hope to patients to get rid of transfusion with the aid of natural products.…”

Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ-globin gene promoter

“…Only roughly half of transfusion dependent β-thalassemia patients are responders with no need of blood transfusion after using HU. On the other hand, about 20% are non-responders who remain transfusion dependent and the rest are partial responders who have increased hemoglobin levels but still need transfusions 7 , 8 . Therefore, many researches have put an effort to find new HbF enhancers with great efficiency and less toxicity.…”

“…However, HU, the only FDA-approved HbF-inducing agent, is not an ideal drug due to drug adverse effects. Moreover, it also exhibits variable responders with an approximately 20–50% partial responders and non-responders in transfusion dependence β-thalassemia patients 7 , 8 . Therefore, new agents that can induce HbF with less or no adverse effects are highly needed.…”