Etude de la variabilité pharmacocinétique du busulfan et évaluation clinique de l'adaptation bayésienne des posologies dans le conditionnement de greffe de moelle osseuse en pédiatrie

Abstract : In order to assess the perfonnance of Bayesian individualization of busulfan (BU) dosage regimens, veno-occlusive disease (YOD) rate was monitored for paediatric patients undergoing allogeneic bone marrow transplantation (BMT). Consecutive patients undergoing allogeneic BMT with BU as conditioning regimen during five years period (January 2000 - Febuary 2006) were reviewed. YOD was major outcome variable. Preconditioning risk ofVOD was estimated for each patient using a scoring system that included type of transplant, recipient CMV-positive status and total parenteral nutrition provided pretransplantation. A risk-adjusted cumulative sum method was used to compare observed versus predicted outcome by assigning a risk score, based on log-likelihood ratios, to each patient. These cumulative scores were sequentially plotted with preset control limits for "signalling" where results were substantially different than expected (doubling or halving of odds ratio). Sixty-six children received BMT after a oral busulfan-based conditioning regimen with median age 3.9 years, 63.6% of male. Median preconditioning risk of YOD was 0.34 range (0.23 - 0.84). Observed YOD rate was 16.7% (n= Il) which was 17 (60.7%) fewer than the expected number estimated by the risk score. The resulting risk-adjusted score for each patient was plotted sequentially. This plot adopt early a negative slope, crossing the lower control limit twice, after 27 and 66 patients, indicating improved results compared to those expected. Bayesian individualization of oral busulfan dosage regimens is useful to reduce YOD rate in children undergoing allogeneic BMT.
Document type :
Theses
Complete list of metadatas

https://hal.univ-lorraine.fr/tel-01776042
Contributor : Administrateur Du Ccsd <>
Submitted on : Tuesday, April 24, 2018 - 3:50:40 PM
Last modification on : Thursday, April 26, 2018 - 1:28:02 AM
Long-term archiving on : Wednesday, September 19, 2018 - 10:38:54 PM

File

SCD_T_2006_0224_BONNET-BERTHOL...
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01776042, version 1

Collections

Citation

Valérie Bonnet-Bertholle. Etude de la variabilité pharmacocinétique du busulfan et évaluation clinique de l'adaptation bayésienne des posologies dans le conditionnement de greffe de moelle osseuse en pédiatrie. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2006. Français. ⟨NNT : 2006NAN12512⟩. ⟨tel-01776042⟩

Share

Metrics

Record views

19

Files downloads

24