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Purpose <p>FLT3 internal tandem duplication (FLT3-ITD) mutations occur frequently in acute myeloid leukemia (AML) and are associated with high relapse risk. Post-transplant gilteritinib (GILT) maintenance is effective in adults, but pediatric dosing, safety, and the role of therapeutic drug monitoring (TDM) remain undefined. This study evaluated the safety, efficacy, and pharmacokinetic variability of GILT in pediatric FLT3-ITD AML, focusing on the relationship between trough concentrations and clinical outcomes.</p> Methods <p>We retrospectively reviewed three pediatric FLT3-ITD AML patients who received post-hematopoietic cell transplantation (HCT) GILT at our institution. Trough plasma concentrations were measured using liquid chromatography–tandem mass spectrometry and correlated with adverse events and remission status.</p> Results <p>A 7-year-old girl developed thrombocytopenia and renal dysfunction at a trough concentration of 372 ng/mL; reduced dosing (20–25&#xa0;mg/day) stabilized levels at 50–60 ng/mL and was tolerated, with sustained remission at three years post-HCT. A 14-year-old girl developed thrombocytopenia at 179 ng/mL and creatine kinase elevation at 205 ng/mL but remained in remission for three years with dose modification and continuation at 40&#xa0;mg/day. A 17-year-old boy tolerated 40&#xa0;mg/day with troughs of 112–162 ng/mL, experiencing only transient, exercise-related creatine kinase elevation, and remains in remission on therapy.</p> Conclusion <p>These cases highlight inter-individual variability in GILT pharmacokinetics and exposure-related toxicities in children. Adverse events correlated with elevated trough concentrations, while levels near or below 100 ng/mL were generally safe. TDM-guided dosing may enable uninterrupted therapy and optimize safety and efficacy of post-transplant GILT maintenance in pediatric FLT3-ITD AML.</p>

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Post-transplantation gilteritinib maintenance therapy and therapeutic drug monitoring in pediatric acute myeloid leukemia with FLT3–internal tandem duplication

  • 期刊论文

  • 发表日期：

    2026年1月20日

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  • Masakatsu Yanagimachi,
  • Reiko Iwano,
  • Dai Keino,
  • Yu Kimizuka,
  • Daisuke Kurita,
  • Akiko Hayashi,
  • Naoyuki Miyagawa,
  • Tomoko Yokosuka,
  • Satoshi Hamanoue,
  • Fuminori Iwasaki,
  • Hiroaki Goto

摘要

Purpose

FLT3 internal tandem duplication (FLT3-ITD) mutations occur frequently in acute myeloid leukemia (AML) and are associated with high relapse risk. Post-transplant gilteritinib (GILT) maintenance is effective in adults, but pediatric dosing, safety, and the role of therapeutic drug monitoring (TDM) remain undefined. This study evaluated the safety, efficacy, and pharmacokinetic variability of GILT in pediatric FLT3-ITD AML, focusing on the relationship between trough concentrations and clinical outcomes.

Methods

We retrospectively reviewed three pediatric FLT3-ITD AML patients who received post-hematopoietic cell transplantation (HCT) GILT at our institution. Trough plasma concentrations were measured using liquid chromatography–tandem mass spectrometry and correlated with adverse events and remission status.

Results

A 7-year-old girl developed thrombocytopenia and renal dysfunction at a trough concentration of 372 ng/mL; reduced dosing (20–25 mg/day) stabilized levels at 50–60 ng/mL and was tolerated, with sustained remission at three years post-HCT. A 14-year-old girl developed thrombocytopenia at 179 ng/mL and creatine kinase elevation at 205 ng/mL but remained in remission for three years with dose modification and continuation at 40 mg/day. A 17-year-old boy tolerated 40 mg/day with troughs of 112–162 ng/mL, experiencing only transient, exercise-related creatine kinase elevation, and remains in remission on therapy.

Conclusion

These cases highlight inter-individual variability in GILT pharmacokinetics and exposure-related toxicities in children. Adverse events correlated with elevated trough concentrations, while levels near or below 100 ng/mL were generally safe. TDM-guided dosing may enable uninterrupted therapy and optimize safety and efficacy of post-transplant GILT maintenance in pediatric FLT3-ITD AML.