title: Combined chelation therapy with deferasirox and deferoxamine in thalassemia.
abstract: Iron overload is the primary cause of mortality and morbidity in thalassemia major despite advances in chelation therapy. We performed a pilot clinical trial to evaluate the safety and efficacy of combined therapy with deferasirox (DFX, 20-30 mg/kg daily) and deferoxamine (DFO, 35-50mg/kg on 3-7 days/week) in 22 patients with persistent iron overload or organ damage. In the 18 subjects completing 12 months of therapy, median liver iron concentration decreased by 31% from 17.4 mg/g (range 3.9-38.2mg/g) to 12.0mg/g (range 0.96-26.7 mg/g, p<0.001). Median ferritin decreased by 24% from 2465 ng/mL (range 1110-10,700 ng/mL) to 1875 ng/mL (range 421-5800 ng/mL, p=0.002). All 6 subjects with elevated myocardial iron showed improvement in MRI T2* (p=0.031). The mean±S.E. plasma non-transferrin-bound iron (NTBI) declined from 3.10±0.25μM to 2.15±0.29μM (p=0.028). The administration of DFX during infusion of DFO further lowered NTBI (-0.28±0.08 μM, p=0.004) and labile plasma iron (LPI, -0.03±0.01 μM, p=0.006). The simultaneous administration of DFO and DFX rapidly reduced systemic and myocardial iron, and provided an excellent control of the toxic labile plasma iron species without an increase in toxicity.
authors.affiliation: Hematology/Oncology, Children's Hospital & Research Center, Oakland, CA 94609, USA. alal@mail.cho.org
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Lal
authors.forename: John
authors.initials: J
authors.lastname: Porter
authors.forename: Nancy
authors.initials: N
authors.lastname: Sweeters
authors.forename: Vivian
authors.initials: V
authors.lastname: Ng
authors.forename: Patricia
authors.initials: P
authors.lastname: Evans
authors.forename: Lynne
authors.initials: L
authors.lastname: Neumayr
authors.forename: Gregory
authors.initials: G
authors.lastname: Kurio
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
mesh_terms: D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage / Q000627:therapeutic use*; D015913:Chelation Therapy; D002648:Child; D000077588:Deferasirox; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007501:Iron / Q000032:analysis; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008099:Liver / Q000737:chemistry; D008297:Male; D009206:Myocardium / Q000737:chemistry; D010865:Pilot Projects; D013789:Thalassemia / Q000150:complications* / Q000378:metabolism; D014168:Transferrin / Q000032:analysis; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014168:Transferrin; D014230:Triazoles; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox