TY - JOUR
T1 - Clinical Impact of Melphalan Pharmacokinetics on Transplantation Outcomes in Children Undergoing Hematopoietic Stem Cell Transplantation
AU - Maemura, Ryo
AU - Wakamatsu, Manabu
AU - Matsumoto, Kana
AU - Sakaguchi, Hirotoshi
AU - Yoshida, Nao
AU - Hama, Asahito
AU - Yoshida, Taro
AU - Miwata, Shunsuke
AU - Kitazawa, Hironobu
AU - Narita, Kotaro
AU - Kataoka, Shinsuke
AU - Ichikawa, Daisuke
AU - Hamada, Motoharu
AU - Taniguchi, Rieko
AU - Suzuki, Kyogo
AU - Kawashima, Nozomu
AU - Nishikawa, Eri
AU - Narita, Atsushi
AU - Okuno, Yusuke
AU - Nishio, Nobuhiro
AU - Kato, Koji
AU - Kojima, Seiji
AU - Morita, Kunihiko
AU - Muramatsu, Hideki
AU - Takahashi, Yoshiyuki
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by management expenses grant from the Ministry of Education, Culture, Sports, Science and Technology.
Publisher Copyright:
© The Author(s) 2022.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - Melphalan is widely used for hematopoietic stem cell transplantation (HSCT) conditioning. However, the relationship between its pharmacokinetic (PK) and transplantation outcomes in children has not been thoroughly investigated. We prospectively analyzed the relationship between melphalan area under the curve (AUC) and transplantation outcome and examined the development of a predictive model for melphalan clearance in children. This study included 43 children aged 0 to 19 years who underwent HSCT following a melphalan-based conditioning regimen from 2017 to 2021. In univariable analysis, high-melphalan AUC resulted in a significantly lower cumulative incidence of acute graft-versus-host disease and a higher cumulative incidence of thrombotic microangiopathy, although no significant difference was observed in survival. Regression analysis of a randomly selected derivation cohort (n = 21) revealed the following covariate PK model: predicted melphalan clearance (mL/min) = 6.47 × 24-h urinary creatinine excretion rate (CER, g/day) × 24-h creatinine clearance rate (CCR, mL/min) + 92.8. In the validation cohort (n = 22), the measured melphalan clearance values were significantly correlated with those calculated based on the prediction equation (R2 = 0.663). These results indicate that melphalan exposure may be optimized by adjusting the melphalan dose according to CER and CCR.
AB - Melphalan is widely used for hematopoietic stem cell transplantation (HSCT) conditioning. However, the relationship between its pharmacokinetic (PK) and transplantation outcomes in children has not been thoroughly investigated. We prospectively analyzed the relationship between melphalan area under the curve (AUC) and transplantation outcome and examined the development of a predictive model for melphalan clearance in children. This study included 43 children aged 0 to 19 years who underwent HSCT following a melphalan-based conditioning regimen from 2017 to 2021. In univariable analysis, high-melphalan AUC resulted in a significantly lower cumulative incidence of acute graft-versus-host disease and a higher cumulative incidence of thrombotic microangiopathy, although no significant difference was observed in survival. Regression analysis of a randomly selected derivation cohort (n = 21) revealed the following covariate PK model: predicted melphalan clearance (mL/min) = 6.47 × 24-h urinary creatinine excretion rate (CER, g/day) × 24-h creatinine clearance rate (CCR, mL/min) + 92.8. In the validation cohort (n = 22), the measured melphalan clearance values were significantly correlated with those calculated based on the prediction equation (R2 = 0.663). These results indicate that melphalan exposure may be optimized by adjusting the melphalan dose according to CER and CCR.
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U2 - 10.1177/09636897221143364
DO - 10.1177/09636897221143364
M3 - Article
C2 - 36537564
AN - SCOPUS:85144286475
VL - 31
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
ER -