Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based dosing in hematopoietic stem cell transplant patients

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Abstract

Busulfan (Bu)-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2 mg/kg/day (FBD) given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring (TDM) of Bu. We compared the Bu dose given using TDM with the FBD of 3.2 mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included. The mean age at transplant was 15 years (range 2–55 years) with 57% adults. Indication for transplantation was leukemia/myelodysplastic syndrome in 46% of the patients, while the remaining 54% were transplanted for inherited blood disorders. We found that the median FBD was lower than the median TDM dose by 39 mg/day with a statistically significant difference (p < 0.001) even after adjusting for the weight (median total FBD of 349 mg, median TDM dose of 494 mg, p < 0.0001). Age and underlying condition (malignant vs. nonmalignant) were the main factors affecting Bu clearance (p < 0.001 and p < 0.07, respectively). TDM remains an important tool for the appropriate dosing of Bu in preparative regimens of hematopoietic stem cell transplantation, especially in populations with genetic admixture.

Original languageEnglish
Pages (from-to)70-78
Number of pages9
JournalHematology/ Oncology and Stem Cell Therapy
Volume10
Issue number2
DOIs
Publication statusPublished - Jun 1 2017

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Busulfan
Drug Monitoring
Hematopoietic Stem Cells
Transplants
Weights and Measures
Hematopoietic Stem Cell Transplantation
Leukemia
beta-Thalassemia
Myelodysplastic Syndromes
Population Genetics
Sickle Cell Anemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Pharmacokinetics
Transplantation
Pharmaceutical Preparations

Keywords

  • Busulfan
  • Drug monitoring
  • Hematopoietic stem cell transplantation
  • Pharmacokinetics

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

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title = "Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based dosing in hematopoietic stem cell transplant patients",
abstract = "Busulfan (Bu)-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2 mg/kg/day (FBD) given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring (TDM) of Bu. We compared the Bu dose given using TDM with the FBD of 3.2 mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included. The mean age at transplant was 15 years (range 2–55 years) with 57{\%} adults. Indication for transplantation was leukemia/myelodysplastic syndrome in 46{\%} of the patients, while the remaining 54{\%} were transplanted for inherited blood disorders. We found that the median FBD was lower than the median TDM dose by 39 mg/day with a statistically significant difference (p < 0.001) even after adjusting for the weight (median total FBD of 349 mg, median TDM dose of 494 mg, p < 0.0001). Age and underlying condition (malignant vs. nonmalignant) were the main factors affecting Bu clearance (p < 0.001 and p < 0.07, respectively). TDM remains an important tool for the appropriate dosing of Bu in preparative regimens of hematopoietic stem cell transplantation, especially in populations with genetic admixture.",
keywords = "Busulfan, Drug monitoring, Hematopoietic stem cell transplantation, Pharmacokinetics",
author = "Bushra Salman and Mohammed Al-Za'abi and Mohammed Al-Huneini and David Dennison and Abdulhakeem Al-Rawas and Salam Al-Kindi and Khalil Al-Farsi and Melanie Tauro and Murtadha Al-Khabori",
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T1 - Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based dosing in hematopoietic stem cell transplant patients

AU - Salman, Bushra

AU - Al-Za'abi, Mohammed

AU - Al-Huneini, Mohammed

AU - Dennison, David

AU - Al-Rawas, Abdulhakeem

AU - Al-Kindi, Salam

AU - Al-Farsi, Khalil

AU - Tauro, Melanie

AU - Al-Khabori, Murtadha

PY - 2017/6/1

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N2 - Busulfan (Bu)-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2 mg/kg/day (FBD) given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring (TDM) of Bu. We compared the Bu dose given using TDM with the FBD of 3.2 mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included. The mean age at transplant was 15 years (range 2–55 years) with 57% adults. Indication for transplantation was leukemia/myelodysplastic syndrome in 46% of the patients, while the remaining 54% were transplanted for inherited blood disorders. We found that the median FBD was lower than the median TDM dose by 39 mg/day with a statistically significant difference (p < 0.001) even after adjusting for the weight (median total FBD of 349 mg, median TDM dose of 494 mg, p < 0.0001). Age and underlying condition (malignant vs. nonmalignant) were the main factors affecting Bu clearance (p < 0.001 and p < 0.07, respectively). TDM remains an important tool for the appropriate dosing of Bu in preparative regimens of hematopoietic stem cell transplantation, especially in populations with genetic admixture.

AB - Busulfan (Bu)-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2 mg/kg/day (FBD) given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring (TDM) of Bu. We compared the Bu dose given using TDM with the FBD of 3.2 mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included. The mean age at transplant was 15 years (range 2–55 years) with 57% adults. Indication for transplantation was leukemia/myelodysplastic syndrome in 46% of the patients, while the remaining 54% were transplanted for inherited blood disorders. We found that the median FBD was lower than the median TDM dose by 39 mg/day with a statistically significant difference (p < 0.001) even after adjusting for the weight (median total FBD of 349 mg, median TDM dose of 494 mg, p < 0.0001). Age and underlying condition (malignant vs. nonmalignant) were the main factors affecting Bu clearance (p < 0.001 and p < 0.07, respectively). TDM remains an important tool for the appropriate dosing of Bu in preparative regimens of hematopoietic stem cell transplantation, especially in populations with genetic admixture.

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