TY - JOUR
T1 - Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation
T2 - a single day versus a multiday therapeutic drug monitoring regimen
AU - Bognàr, T. (Tim)
AU - Kingma, J.S. (Jurjen)
AU - Smeijsters, E. H.(Erin)
AU - van der Elst, K. C.M.(Kim)
AU - de Kanter, C. T.M.(Klaartje)
AU - Lindemans, C. A.(Caroline)
AU - Egberts, A. C.G.(Toine)
AU - Bartelink, I. H.(Imke)
AU - Lalmohamed, A. (Arief)
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/7
Y1 - 2023/7
N2 - Busulfan exposure has previously been linked to clinical outcomes, hence the need for therapeutic drug monitoring (TDM). Study objective was to evaluate the effect of day 1 TDM-guided dosing (regimen d1) versus days 1 + 2 TDM-guided dosing (regimen d1 + 2) on attaining adequate busulfan exposure. In this observational study, we included all children receiving busulfan-based allogeneic hematopoietic cell transplantation. Primary outcome was the percentage of patients achieving busulfan target attainment in both TDM regimens. Secondary outcomes were the variance in busulfan exposure and day-4 clearance (Clday4) estimates between both TDM regimens and dosing day 1 and 2. In regimen d1, 84.3% (n = 91/108) attained a therapeutic busulfan exposure, while in regimen d1 + 2 a proportion of 90.9% was found (n = 30/33, not-significant). Variance of Clday4 estimate based on busulfan day 2 concentrations was significantly smaller than the variance of Clday4 estimates based on day 1 concentrations (p < 0.001). Therefore, day 1-guided TDM (pharmacometric model-based) of busulfan may be sufficient for attaining optimal target exposure, provided that subsequent TDM is carried out if required. However, performing TDM on subsequent days may be beneficial, as measurements on day 2 seemed to reduce the variance in the estimated clearance as compared to day 1 sampling.
AB - Busulfan exposure has previously been linked to clinical outcomes, hence the need for therapeutic drug monitoring (TDM). Study objective was to evaluate the effect of day 1 TDM-guided dosing (regimen d1) versus days 1 + 2 TDM-guided dosing (regimen d1 + 2) on attaining adequate busulfan exposure. In this observational study, we included all children receiving busulfan-based allogeneic hematopoietic cell transplantation. Primary outcome was the percentage of patients achieving busulfan target attainment in both TDM regimens. Secondary outcomes were the variance in busulfan exposure and day-4 clearance (Clday4) estimates between both TDM regimens and dosing day 1 and 2. In regimen d1, 84.3% (n = 91/108) attained a therapeutic busulfan exposure, while in regimen d1 + 2 a proportion of 90.9% was found (n = 30/33, not-significant). Variance of Clday4 estimate based on busulfan day 2 concentrations was significantly smaller than the variance of Clday4 estimates based on day 1 concentrations (p < 0.001). Therefore, day 1-guided TDM (pharmacometric model-based) of busulfan may be sufficient for attaining optimal target exposure, provided that subsequent TDM is carried out if required. However, performing TDM on subsequent days may be beneficial, as measurements on day 2 seemed to reduce the variance in the estimated clearance as compared to day 1 sampling.
KW - Busulfan
KW - Child
KW - Drug Monitoring
KW - Hematopoietic Stem Cell Transplantation
KW - Humans
KW - Transplantation Conditioning
UR - http://www.scopus.com/inward/record.url?scp=85151476760&partnerID=8YFLogxK
U2 - 10.1038/s41409-023-01971-z
DO - 10.1038/s41409-023-01971-z
M3 - Article
C2 - 37002411
AN - SCOPUS:85151476760
SN - 0268-3369
VL - 58
SP - 762
EP - 768
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 7
ER -