Association Between Busulfan Exposure and Outcome in Children Receiving Intravenous Busulfan Before Hematopoietic Stem Cell Transplantation

@article{Ansari2014AssociationBB,
  title={Association Between Busulfan Exposure and Outcome in Children Receiving Intravenous Busulfan Before Hematopoietic Stem Cell Transplantation},
  author={Marc Ansari and Yves Th{\'e}or{\^e}t and Mohamed Aziz Rezgui and Christina Peters and Samira Mezziani and Catherine Desjean and Marie France Vachon and Martin A. Champagne and Michel Duval and Maja Krajinovic and Henrique Bittencourt},
  journal={Therapeutic Drug Monitoring},
  year={2014},
  volume={36},
  pages={93–99}
}
Background and Objective: Intravenous (IV) busulfan (Bu) combined with therapeutic drug monitoring-guided dosing is associated with better event-free survival (EFS), lower transplant-related mortality. But optimal target steady-state concentration (Css) of Bu in children undergoing hematopoietic stem cell transplantation (HSCT) remains unclear. This study aimed to evaluate the relation between Css of Bu and clinical outcomes in children receiving Bu before HSCT. Methods: This study includes 75… 
Clinical outcomes of individualized busulfan-dosing in hematopoietic stem cell transplantation in Chinese children undergoing with therapeutic drug monitoring
TLDR
Therapeutic drug monitoring (TDM) and individualization of Bu dosage are essential to improve the efficacy and safety of busulfan-based regimen in Chinese pediatric HSCT recipients.
Personalized pharmacokinetic targeting with busulfan in allogeneic hematopoietic stem cell transplantation in infants with acute lymphoblastic leukemia
TLDR
The clinical outcome of engraftment, graft-versus-host disease, adverse events, including sinusoidal obstruction syndrome, and survival did not correlate with the BU PK data, which paradoxically suggests that remaining within this Css range helped minimize transplant-related toxicities, while securing engraftments in infants with MLL-r ALL.
Pharmacokinetics-adapted Busulfan-based myeloablative conditioning before unrelated umbilical cord blood transplantation for myeloid malignancies in children
TLDR
For children with high risk myeloid malignancies receiving an UCBT, first dose Bu pharmacokinetic seems to be a significant prognostic factor, influencing neutrophil and platelet recovery and non-relapse mortality, and reinforcing the importance of Busulfan therapeutic drug monitoring-guided dosing in pediatric HSCT patients, particularly in the context of UCBT.
Therapeutic Drug Monitoring of Busulfan for the Management of Pediatric Patients: Cross-Validation of Methods and Long-Term Performance
TLDR
The utility of therapeutic drug monitoring (TDM) of Bu in children, the reliability of Bu quantification methods, and its stability in plasma when stored for up to 5 years are assessed.
Single Daily Busulfan Dosing for Infants with Nonmalignant Diseases Undergoing Reduced-Intensity Conditioning for Allogeneic Hematopoietic Progenitor Cell Transplantation.
  • J. Ward, M. Kletzel, W. Tse
  • Medicine
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2015
Busulfan Pharmacokinetics and Precision Dosing: Are Patients with Fanconi Anemia Different?
  • P. Mehta, C. Emoto, F. Boulad
  • Medicine
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2019
Use of an Oral Busulfan Test Dose in Patients Undergoing Hematopoietic Stem Cell Transplantation Treated With or Without Fludarabine
TLDR
The results suggest that in concomitant administration of FLU and BU during conditioning regimens for HSCT, changes in BU dose should be considered only after the administration of the fifth BU dose.
GSTA1 Genetic Variants and Conditioning Regimen: Missing Key Factors in Dosing Guidelines of Busulfan in Pediatric Hematopoietic Stem Cell Transplantation.
  • T. Nava, M. A. Rezgui, H. Bittencourt
  • Medicine, Biology
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2017
Performance of Busulfan Dosing Guidelines for Pediatric Hematopoietic Stem Cell Transplant Conditioning.
  • J. Zao, T. Schechter, L. Dupuis
  • Medicine
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2015
...
...

References

SHOWING 1-10 OF 51 REFERENCES
Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematologic stem cell transplantation.
  • I. Bartelink, R. Bredius, J. Boelens
  • Medicine, Biology
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2009
Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation
TLDR
Targeting Bu Css ranges of 600–900 ng/ml significantly improved the rate of successful engraftment from 74% to 94% and indicates that targeted busulfan dosing optimizes allogeneic engraftedment in children.
Intravenous busulfan in children prior to stem cell transplantation: study of pharmacokinetics in association with early clinical outcome and toxicity
TLDR
It is concluded that, in accordance with previous data, within the observed AUCs no clear relationship was observed between Bu AUC and outcome with respect to toxicity, engraftment and relapse.
Busulfan concentration and graft rejection in pediatric patients undergoing hematopoietic stem cell transplantation
TLDR
It may be possible to improve the outcome of HSCT in pediatric patients receiving the BU/CY regimen through optimization of busulfan CSS and better definition of the contribution of activated cyclophosphamide metabolites to toxicity.
Intravenous busulfan for allogeneic hematopoietic stem cell transplantation in infants: clinical and pharmacokinetic results
TLDR
This study demonstrates that a cumulative dosage of 16 mg/kg is associated with higher exposure than expected in infants, and suggests an initial dose of 0.8  mg/kg followed by pharmacokinetically guided dose adjustment.
Individualizing high-dose oral busulfan: prospective dose adjustment in a pediatric population undergoing allogeneic stem cell transplantation for advanced hematologic malignancies
TLDR
The feasibility of adjusting the oral BU dose in individual pediatric patients is demonstrated and toxicity associated with BU seemed to be reduced, but the overall regimen-related toxicity (RRT) remains substantial and reflected the effects of all agents used in the preparative regimen.
Pharmacokinetic disposition and clinical outcomes in infants and children receiving intravenous busulfan for allogeneic hematopoietic stem cell transplantation.
  • T. Schechter, Y. Finkelstein, L. Dupuis
  • Medicine, Biology
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2007
Intravenous busulfan in adults prior to haematopoietic stem cell transplantation: a population pharmacokinetic study
TLDR
A limited sampling strategy based on a Bayesian methodology was developed and validated on an independent dataset: AUCs obtained from one to two samplings were demonstrated to be reliably estimated and no dose adjustment is required in obese patients when using a AIBW- or BSA-based dose calculation.
Busulfan pharmacokinetics do not predict relapse in acute myeloid leukemia
TLDR
Pharmacokinetic dosing of BU may be important for prevention of NRM but does not appear to influence the risk of relapse in this largely pediatric population with AML.
Fludarabine and pharmacokinetic-targeted busulfan before allografting for adults with acute lymphoid leukemia.
  • S. Santarone, J. Pidala, C. Anasetti
  • Medicine, Biology
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2011
...
...