ArticleTherapeutic drug monitoring2015
Population pharmacokinetics of busulfan in pediatric and young adult patients undergoing hematopoietic cell transplant: a model-based dosing algorithm for personalized therapy and implementation into routine clinical use.
Article in Therapeutic drug monitoring, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03538899 (Phase I/II Safety and Efficacy Study of Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency), which is not on this map. Cited by 44 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase I/II Safety and Efficacy Study of Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency (ART-SCID) in Newly Diagnosed Patients Using Self-Inactivating Lentiviral Vector (AProArt) to Transduce Autologous CD34 Hematopoietic Cells
Who cites it
44 citing papers in PubMed, 4 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- Barriers and Facilitators for Bringing Model-Informed Precision Dosing to the Patient's Bedside: A Systematic Review.Clinical pharmacology and therapeutics · 2025Pooled it
- A practical guide to therapeutic drug monitoring in busulfan: recommendations from the Pharmacist Committee of the European Society for Blood and Marrow Transplantation (EBMT).Bone marrow transplantation · 2024Guideline
- Population Pharmacokinetic Model of Intravenous Busulfan in Hematopoietic Cell Transplantation: Systematic Review and Comparative Simulations.Clinical pharmacokinetics · 2023Pooled it
- Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance.European journal of cancer (Oxford, England : 1990) · 2022Pooled it
- Clinical outcomes of individualized busulfan-dosing in hematopoietic stem cell transplantation in Chinese children undergoing with therapeutic drug monitoring.Bone marrow transplantation · 2022Trial
- Low Exposure Busulfan Conditioning to Achieve Sufficient Multilineage Chimerism in Patients with Severe Combined Immunodeficiency.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2019Trial
- Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1.The New England journal of medicine · 2019Trial
- Comparing the Predictive Performance of Machine Learning Models with a Newly Developed Population Pharmacokinetic Model for Busulfan in Paediatric Patients.Clinical pharmacokinetics · 2026Article
- Busulfan pharmacokinetics in adults - a real-world evaluation of intra-individual variability and the impact of obesity and deferasirox.Bone marrow transplantation · 2026Article
- Mathematical Oncology: How Modeling Is Transforming Clinical Decision-Making.Cancer research · 2025Review
- Review
- Semi-mechanistic population pharmacokinetic model incorporating glutathione S-transferase activity for personalized busulfan dosing in pediatric allogeneic hematopoietic cell transplantation.Frontiers in pharmacology · 2025Article
- Article
- Article
- Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation: a single day versus a multiday therapeutic drug monitoring regimen.Bone marrow transplantation · 2023Observational
- Development and Validation of a Novel LC-MS/MS Method for a TDM-Guided Personalization of HSCT Conditioning with High-Dose Busulfan in Children.Biomedicines · 2023Article
- Population pharmacokinetic model for once-daily intravenous busulfan in pediatric subjects describing time-associated clearance.CPT: pharmacometrics & systems pharmacology · 2022Article
- Population Pharmacokinetics of Busulfan and Its Metabolite Sulfolane in Patients with Myelofibrosis Undergoing Hematopoietic Stem Cell Transplantation.Pharmaceutics · 2022Article
- External Evaluation of Population Pharmacokinetic Models of Busulfan in Chinese Adult Hematopoietic Stem Cell Transplantation Recipients.Frontiers in pharmacology · 2022Article
- Can First-Dose Therapeutic Drug Monitoring Predict the Steady State Area Under the Blood Concentration-Time Curve of Busulfan in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation?Frontiers in pediatrics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundPopulation pharmacokinetic (PK) studies of busulfan in children have shown that individualized model-based algorithms provide improved targeted busulfan therapy when compared with conventional dose guidelines. The adoption of population PK models into routine clinical practice has been hampered by the tendency of pharmacologists to develop complex models too impractical for clinicians to use. The authors aimed to develop a population PK model for busulfan in children that can reliably achieve therapeutic exposure (concentration at steady state) and implement a simple model-based tool for the initial dosing of busulfan in children undergoing hematopoietic cell transplantation. PATIENTS AND
methodsModel development was conducted using retrospective data available in 90 pediatric and young adult patients who had undergone hematopoietic cell transplantation with busulfan conditioning. Busulfan drug levels and potential covariates influencing drug exposure were analyzed using the nonlinear mixed effects modeling software, NONMEM. The final population PK model was implemented into a clinician-friendly Microsoft Excel-based tool and used to recommend initial doses of busulfan in a group of 21 pediatric patients prospectively dosed based on the population PK model.
resultsModeling of busulfan time-concentration data indicates that busulfan clearance displays nonlinearity in children, decreasing up to approximately 20% between the concentrations of 250-2000 ng/mL. Important patient-specific covariates found to significantly impact busulfan clearance were actual body weight and age. The percentage of individuals achieving a therapeutic concentration at steady state was significantly higher in subjects receiving initial doses based on the population PK model (81%) than in historical controls dosed on conventional guidelines (52%) (P = 0.02).
conclusionsWhen compared with the conventional dosing guidelines, the model-based algorithm demonstrates significant improvement for providing targeted busulfan therapy in children and young adults.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.