One-year results from a prospective randomized trial comparing phlebotomy with deferasirox for the treatment of iron overload in pediatric patients with thalassemia major following curative stem cell transplantation.

Abstract

BACKGROUND:

Iron overload is well documented in patients with β-thalassemia major, and patients who have undergone hematopoietic stem cell transplantation (HSCT) remain at risk as a result of pre- and immediate post-HSCT transfusions.

PROCEDURE:

This is a prospective, randomized, 1-year clinical trial that compares the efficacy and safety of the once-daily oral iron chelator deferasirox versus phlebotomy for the treatment of iron overload in children with β-thalassemia major following HSCT.

RESULTS:

Patients (aged 12.4 years) received deferasirox (n = 12, 10 mg/kg/day starting dose) or phlebotomy (n = 14, 6 ml/kg/2 weeks) for 1 year. In two and five patients, deferasirox dose was increased to 15 and 20 mg/kg/day, respectively. Magnetic resonance imaging (MRI)-assessed liver iron concentration (LIC) decreased with deferasirox (mean 12.5 ± 10.1 to 8.5 ± 9.3 mg Fe/g dry weight [dw]; P = 0.0005 vs. baseline) and phlebotomy (10.2 ± 6.8 to 8.3 ± 9.2 mg Fe/g dw; P = 0.05). LIC reductions were greater with deferasirox than with phlebotomy for patients with baseline serum ferritin 1,000 ng/ml or higher (-8.1 ± 1.5 vs. -3.5 ± 5.7 mg Fe/g dw; P = 0.048). Serum ferritin and non-transferrin-bound iron also decreased significantly. In two patients with severe cardiac siderosis, a clinically relevant improvement in myocardial T2* was seen, following phlebotomy and deferasirox therapy (n = 1 each). Adverse effects with deferasirox were skin rash, gastrointestinal upset, and increased liver function tests (all n = 1), while those for phlebotomy were difficulty with venous access (n = 4) and distress during procedure (n = 1). Parents of 13/14 children receiving phlebotomy wished to switch to deferasirox, with 1/14 being satisfied with phlebotomy.

CONCLUSIONS:

Deferasirox treatment or phlebotomy reduces iron burden in pediatric patients with β- thalassemia major post-HSCT, with a manageable safety profile.

• Authors: Adlette Inati, Mario Kahale, Nada Sbeiti, Maria Domenica Cappellini, Ali T Taher, Suzanne Koussa, Therese A Nasr, Khaled M Musallam, Hussein A Abbas, John B Porter
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 64 Issue 1 Pg. 188-196 (01 2017) ISSN: 1545-5017 [Electronic] United States
• PMID: 27576370 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• Benzoates
• Iron Chelating Agents
• Triazoles
• Deferasirox

Topics

• Adolescent
• Benzoates (therapeutic use)
• Child
• Child, Preschool
• Combined Modality Therapy
• Deferasirox
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Iron Chelating Agents (therapeutic use)
• Iron Overload (diagnosis, etiology, therapy)
• Male
• Phlebotomy (methods)
• Prognosis
• Prospective Studies
• Triazoles (therapeutic use)
• beta-Thalassemia (therapy)