title: The deferiprone and deferasirox combination is efficacious in iron overloaded patients with β-thalassemia major: A prospective, single center, open-label study.
abstract: BACKGROUND
  The high cost, coupled with the need for continuous infusion, renders Desferrioxamine (DFO), a non-feasible option for iron-chelation in a large majority of patients with β-thalassemia major in developing countries. Monotherapy with deferiprone (DFP) or deferasirox (DFX) may not always attain optimal control, particularly in heavily iron-loaded patients. Combination of DFP and DFX is a potential alternative.
  
  
  METHODS
  A prospective, single-center, open-label, uncontrolled study was conducted to evaluate the safety and efficacy of the combination in patients with β-thalassemia major. Patients who had received either DFP or DFX for >1 year and a serum ferritin >2,000 μg/L were enrolled. Blood counts, liver/renal functions, and serum ferritin were monitored during the 1-year study period. Facilities for cardiac T2*-MRI were unavailable.
  
  
  RESULTS
  Thirty-six patients with a mean age of 13 ± 6.9 years (range: 4-29) and a ferritin of 6,768 ± 4,145 μg/L formed the study cohort. Eight (22%) patients had transient gastrointestinal adverse effects. DFX was discontinued in one patient for persistent abdominal pain/diarrhea. Eight (22%) had joint symptoms; DFP was discontinued in two. Four (11%) patients had elevation in AST/ALT levels, managed with temporary interruption of DFX. Nine (25%) had an inconsistent elevation of creatinine to >33% of baseline; no intervention was done. One had transient proteinuria. None had neutropenia. At the end of 1 year, the serum ferritin reduced by a mean value of 3,275.3 ± 618.2 μg/L (P < 0.001).
  
  
  CONCLUSIONS
  The oral combination was found to be safe, efficacious, and a feasible option in patients with suboptimal response to monotherapy.
authors.affiliation: Department of Pediatrics, Hematology-Oncology Unit and Biochemistry, Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Sidharth
authors.initials: S
authors.lastname: Totadri
authors.affiliation: Department of Pediatrics, Hematology-Oncology Unit and Biochemistry, Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bansal
authors.affiliation: Department of Pediatrics, Hematology-Oncology Unit and Biochemistry, Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Prateek
authors.initials: P
authors.lastname: Bhatia
authors.affiliation: Department of Pediatrics, Hematology-Oncology Unit and Biochemistry, Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Savita V
authors.initials: SV
authors.lastname: Attri
authors.affiliation: Department of Pediatrics, Hematology-Oncology Unit and Biochemistry, Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Amita
authors.initials: A
authors.lastname: Trehan
authors.affiliation: Department of Pediatrics, Hematology-Oncology Unit and Biochemistry, Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: R K
authors.initials: RK
authors.lastname: Marwaha
mesh_terms: D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015913:Chelation Therapy / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D000077543:Deferiprone; D003875:Drug Eruptions / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D005293:Ferritins / Q000097:blood; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology; D007592:Joint Diseases / Q000139:chemically induced; D008297:Male; D011446:Prospective Studies; D011507:Proteinuria / Q000139:chemically induced; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D065227:Transfusion Reaction; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood / Q000150:complications* / Q000628:therapy
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D011728:Pyridones; D014230:Triazoles; D000077543:Deferiprone; D005293:Ferritins; D007501:Iron; D000077588:Deferasirox
keywords: India; arthropathy; chelation; desferal; exjade