Safety and tolerability of deferasirox in pediatric hematopoietic stem cell transplant recipients

One facility's five years' experience of chelation treatment

Natalia Maximova, Massimo Gregori, Roberto Simeone, Aurelio Sonzogni, Giulia Boz, Carmen Fucile, Valeria Marini, Antonietta Martelli, Francesca Mattioli

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

42 pediatric patients with iron overload, who underwent liver biopsy and DFX treatment after hematopoietic stem cell transplantation were included in the study group. The patients were divided into two groups diversified according to deferasirox trough plasma concentrations (DFX Ctrough) with cut-off equal to10 mcg/mL. The average dose of DFX was 25.9 mg/kg in the DFX Ctrough < 10 mcg/mL group versus 19.2 mg/kg in the DFX Ctrough > 10 mcg/mL group (p=0,0003). The mean duration of DFX treatment was 135.7 days in the DFX Ctrough < 10 mcg/mL group versus 41.8 days in the DFX Ctrough > 10 mcg/mL group (p < 0.0001). The mean tissue iron concentration in the DFX Ctrough < 10 mcg/mL group was 261.9 μmol/g versus 133.4 μmol/g in the DFX Ctrough > 10 mcg/mL group (p < 0.0001). 21 patients (100%) in the DFX Ctrough > 10 mcg/mL group had ductopenia which was complete in 47.6% of them and severe in 52.4%. All patients with particularly high Ctrough ( > 25 mcg/mL) were found to have total ductopenia. 90.5% of all deferasirox-related adverse events and 100% of major adverse events occurred in the DFX Ctrough > 10 mcg/mL group. In the DFX Ctrough < 10 mcg/mL group only one patient interrupted chelation therapy versus 16 (84.2%) patients in the DFX Ctrough > 10 mcg/mL group. We would recommend a close monitoring in pediatric hematopoietic transplant recipients subjected to deferasiroxbased therapy because we have observed a high incidence of adverse events and discontinuation of chelation treatment.

Original languageEnglish
Pages (from-to)63177-63186
Number of pages10
JournalOncotarget
Volume8
Issue number38
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Hematopoietic Stem Cells
Pediatrics
Transplants
Safety
Iron Overload
Hematopoietic Stem Cell Transplantation
Therapeutics
Biopsy
deferasirox
Transplant Recipients
Liver
Incidence

Keywords

  • Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
  • Deferasirox
  • Ductopenia
  • Pediatric
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Oncology

Cite this

Safety and tolerability of deferasirox in pediatric hematopoietic stem cell transplant recipients : One facility's five years' experience of chelation treatment. / Maximova, Natalia; Gregori, Massimo; Simeone, Roberto; Sonzogni, Aurelio; Boz, Giulia; Fucile, Carmen; Marini, Valeria; Martelli, Antonietta; Mattioli, Francesca.

In: Oncotarget, Vol. 8, No. 38, 01.01.2017, p. 63177-63186.

Research output: Contribution to journalArticle

Maximova, Natalia ; Gregori, Massimo ; Simeone, Roberto ; Sonzogni, Aurelio ; Boz, Giulia ; Fucile, Carmen ; Marini, Valeria ; Martelli, Antonietta ; Mattioli, Francesca. / Safety and tolerability of deferasirox in pediatric hematopoietic stem cell transplant recipients : One facility's five years' experience of chelation treatment. In: Oncotarget. 2017 ; Vol. 8, No. 38. pp. 63177-63186.
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abstract = "42 pediatric patients with iron overload, who underwent liver biopsy and DFX treatment after hematopoietic stem cell transplantation were included in the study group. The patients were divided into two groups diversified according to deferasirox trough plasma concentrations (DFX Ctrough) with cut-off equal to10 mcg/mL. The average dose of DFX was 25.9 mg/kg in the DFX Ctrough < 10 mcg/mL group versus 19.2 mg/kg in the DFX Ctrough > 10 mcg/mL group (p=0,0003). The mean duration of DFX treatment was 135.7 days in the DFX Ctrough < 10 mcg/mL group versus 41.8 days in the DFX Ctrough > 10 mcg/mL group (p < 0.0001). The mean tissue iron concentration in the DFX Ctrough < 10 mcg/mL group was 261.9 μmol/g versus 133.4 μmol/g in the DFX Ctrough > 10 mcg/mL group (p < 0.0001). 21 patients (100{\%}) in the DFX Ctrough > 10 mcg/mL group had ductopenia which was complete in 47.6{\%} of them and severe in 52.4{\%}. All patients with particularly high Ctrough ( > 25 mcg/mL) were found to have total ductopenia. 90.5{\%} of all deferasirox-related adverse events and 100{\%} of major adverse events occurred in the DFX Ctrough > 10 mcg/mL group. In the DFX Ctrough < 10 mcg/mL group only one patient interrupted chelation therapy versus 16 (84.2{\%}) patients in the DFX Ctrough > 10 mcg/mL group. We would recommend a close monitoring in pediatric hematopoietic transplant recipients subjected to deferasiroxbased therapy because we have observed a high incidence of adverse events and discontinuation of chelation treatment.",
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