Therapeutic superiority and safety of combined hydroxyurea with recombinant human erythropoietin over hydroxyurea in young β-thalassemia intermedia patients

Eur J Haematol. 2013 Dec;91(6):522-33. doi: 10.1111/ejh.12182. Epub 2013 Oct 5.

Abstract

Objective: To assess the efficacy and safety of combined hydroxyurea (HU) and recombinant human erythropoietin (rHuEPO) in β-thalassemia intermedia (TI) patients compared with single HU therapy.

Methods: An interventional prospective randomized study registered in the ClinicalTrials.gov (NCT01624038) was performed on 80 TI patients (≤ 18 yr) divided into group A (40 patients received combined HU and rHuEPO) and group B (40 patients received single HU therapy). Baseline serum EPO levels were measured, and both groups were followed up for a mean period of 1 yr with regular assessment of transfusion requirements, blood pressure, ferritin, liver and renal functions, hemoglobin, and HbF. Quality of life (QoL) was assessed at the start and end of the study.

Results: Transfusion frequency and index were significantly decreased, while QoL was increased in group A compared with group B where 85% of patients showed improvement on combined therapy compared with 50% of patients on HU. Hemoglobin and HbF were significantly increased in both TI groups; however, this was more evident in group A than in group B. Also, 37.5% of patients in group A became transfusion-independent compared with 15% in group B. EPO levels were negatively related to increments of hemoglobin and HbF. Splenectomized patients and those with initial HbF% >40% had the best response to combined therapy. No serious adverse events necessitating discontinuation of therapy in both groups.

Conclusions: HU was effective in management of TI; however, combination with rHuEPO gave a superior therapeutic effect resulting in the best clinical and hematological responses without adverse events.

Keywords: combined therapy; erythropoietin; hydroxyurea; quality of life; thalassemia intermedia.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Age Factors
  • Blood Transfusion
  • Child
  • Drug Therapy, Combination
  • Erythropoietin / administration & dosage
  • Erythropoietin / adverse effects
  • Erythropoietin / therapeutic use*
  • Female
  • Follow-Up Studies
  • Hemoglobins / metabolism
  • Humans
  • Hydroxyurea / administration & dosage
  • Hydroxyurea / adverse effects
  • Hydroxyurea / therapeutic use*
  • Male
  • Recombinant Proteins
  • Risk Factors
  • Treatment Outcome
  • beta-Thalassemia / diagnosis
  • beta-Thalassemia / drug therapy*
  • beta-Thalassemia / therapy

Substances

  • Hemoglobins
  • Recombinant Proteins
  • Erythropoietin
  • Hydroxyurea

Associated data

  • ClinicalTrials.gov/NCT01624038