Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation: a single day versus a multiday therapeutic drug monitoring regimen (2024)

Bognàr, T., Kingma, J. S., Smeijsters, E. H., van der Elst, K. C. M., de Kanter, C. T. M., Lindemans, C. A., Egberts, A. C. G., Bartelink, I. H. (2023). Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation: a single day versus a multiday therapeutic drug monitoring regimen. Bone Marrow Transplantation, 58(7), 762-768. https://doi.org/10.1038/s41409-023-01971-z

Bognàr, T. (Tim) ; Kingma, J.S. (Jurjen) ; Smeijsters, E. H.(Erin) et al. / Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation : a single day versus a multiday therapeutic drug monitoring regimen. In: Bone Marrow Transplantation. 2023 ; Vol. 58, No. 7. pp. 762-768.

@article{a0efab1fb70a4bb29d16d96ce6c310dd,

title = "Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation: a single day versus a multiday therapeutic drug monitoring regimen",

abstract = "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 (pharmacometricmodel-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.",

keywords = "Busulfan, Child, Drug Monitoring, Hematopoietic Stem Cell Transplantation, Humans, Transplantation Conditioning",

author = "Bogn{\`a}r, {T. (Tim)} and Kingma, {J.S. (Jurjen)} and Smeijsters, {E. H.(Erin)} and {van der Elst}, {K. C.M.(Kim)} and {de Kanter}, {C. T.M.(Klaartje)} and Lindemans, {C. A.(Caroline)} and Egberts, {A. C.G.(Toine)} and Bartelink, {I. H.(Imke)} and Lalmohamed, {A. (Arief)}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2023",

month = jul,

doi = "10.1038/s41409-023-01971-z",

language = "English",

volume = "58",

pages = "762--768",

journal = "Bone Marrow Transplantation",

issn = "0268-3369",

publisher = "Nature Publishing Group",

number = "7",

}

Bognàr, T, Kingma, JS, Smeijsters, EH, van der Elst, KCM, de Kanter, CTM, Lindemans, CA, Egberts, ACG, Bartelink, IH 2023, 'Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation: a single day versus a multiday therapeutic drug monitoring regimen', Bone Marrow Transplantation, vol. 58, no. 7, pp. 762-768. https://doi.org/10.1038/s41409-023-01971-z

Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation: a single day versus a multiday therapeutic drug monitoring regimen. / Bognàr, T. (Tim); Kingma, J.S. (Jurjen); Smeijsters, E. H.(Erin) et al.
In: Bone Marrow Transplantation, Vol. 58, No. 7, 07.2023, p. 762-768.

Research output: Contribution to journal › Article › Academic › peer-review

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 (pharmacometricmodel-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 (pharmacometricmodel-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.

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KW - Child

KW - Drug Monitoring

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Transplantation Conditioning

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DO - 10.1038/s41409-023-01971-z

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Bognàr T, Kingma JS, Smeijsters EH, van der Elst KCM, de Kanter CTM, Lindemans CA et al. Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation: a single day versus a multiday therapeutic drug monitoring regimen. Bone Marrow Transplantation. 2023 Jul;58(7):762-768. Epub 2023 Mar 31. doi: 10.1038/s41409-023-01971-z