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High interpatient variability of treosulfan exposure is associated with early toxicity in paediatric HSCT: a

M Y Eileen C van der Stoep1, Alice Bertaina2, Marloes H Ten Brink1

  • 1Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, the Netherlands.

British Journal of Haematology
|October 20, 2017
PubMed

Insights

Treosulfan pharmacokinetics show high variability in children undergoing hematopoietic stem cell transplantation (HSCT). Higher treosulfan exposure is linked to increased mucosal and skin toxicity, but not early clinical outcomes.

Area of Science:

  • Pharmacology
  • Pediatric Oncology
  • Hematology

Background:

  • Treosulfan-based conditioning is common in pediatric hematopoietic stem cell transplantation (HSCT).
  • Limited data exist on treosulfan pharmacokinetics and toxicity in children.
  • The relationship between treosulfan exposure and clinical outcomes in pediatric HSCT remains unclear.

Purpose of the Study:

  • To investigate treosulfan pharmacokinetics in pediatric HSCT patients.
  • To determine the association between treosulfan exposure, toxicity, and early clinical outcomes.
  • To analyze inter-individual variability in treosulfan exposure.

Main Methods:

  • A multicenter prospective observational study involving 77 pediatric patients.
  • Dosage adjusted for age: 30 g/m² for infants <1 year, 42 g/m² for children ≥1 year.
  • Measured day 1 treosulfan exposure and assessed regimen-related toxicity and early clinical outcomes.

Main Results:

  • Significant inter-individual variability in treosulfan exposure was observed (56% in infants, 33% in older children).
  • High treosulfan exposure (>1650 mg*h/l) correlated with increased risk of mucosal and skin toxicity.
  • No correlation found between treosulfan exposure and engraftment, acute graft-versus-host disease, or donor chimerism.

Conclusions:

  • This study provides the first evidence of high treosulfan pharmacokinetic variability in pediatric HSCT.
  • Increased treosulfan exposure is associated with early toxicity in pediatric patients.
  • Further research is needed to determine the long-term impact of treosulfan exposure on outcomes.

Keywords:
conditioning regimenpaediatricspharmacokineticstoxicitytreosulfan

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