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Busulfan dosing in children with BMIs ≥ 85% undergoing HSCT: a new optimal strategy.
Biol Blood Marrow Transplant. 2011 Sep; 17(9):1383-8.BB

Abstract

Childhood obesity has more than tripled in the past 30 years. The prevalence of overweight and obese children has also increased in the pediatric cancer setting, causing substantial concern over proper chemotherapeutic dosing in this population. The purpose of this study was to determine if children with an increased body mass index (BMI) have an alteration in busulfan pharmacokinetics during hematopoietic stem cell transplant (HSCT) conditioning. We retrospectively reviewed data on busulfan pharmacokinetics (PK) on HSCT subjects (subjects were part of a prospective study previously reported by our group at Children's Memorial Hospital) to determine appropriateness of dosing. Subjects were divided into appropriate BMI categories (<25th percentile, 25th-85th percentile, ≥ 85th percentile) and busulfan PK dosing was analyzed (test dose, regimen dose, area under the curve [AUC], and clearance). The dosing based on PK test dose data of children with BMI ≥ 85% was compared against the package insert dosing recommendations of using adjusted ideal body weight (AIBW) in obese patients to determine which dosing schema was most accurate. Children with high BMIs had higher AUCs when dosing on actual weight then their normal or low BMI counterparts. This indicates that children with a high BMI require less drug (2.9 mg/kg using actual body weight) to achieve the same AUC as children with normal BMI (4.0 mg/kg) or low BMI (3.6 mg/kg). Using the recommended AIBW dosing schema, 53% of the patients with high BMIs would have had regimen dose AUCs ≥ 20% over/under the target; whereas with the PK test dose method, only 16% of the patients with high BMIs had regimen dose AUCs ≥ 20% over/under the target. PK testing continues to be the gold standard for busulfan dosing in children. Particular vigilance should be paid to PK monitoring in high BMI categories because of the potential risk of imprecise dosing when using the AIBW schema.

Authors+Show Affiliations

University of Utah, School of Medicine, Department of Pediatrics, Salt Lake City, Utah, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21288495

Citation

Browning, Brittan, et al. "Busulfan Dosing in Children With BMIs ≥ 85% Undergoing HSCT: a New Optimal Strategy." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 17, no. 9, 2011, pp. 1383-8.
Browning B, Thormann K, Donaldson A, et al. Busulfan dosing in children with BMIs ≥ 85% undergoing HSCT: a new optimal strategy. Biol Blood Marrow Transplant. 2011;17(9):1383-8.
Browning, B., Thormann, K., Donaldson, A., Halverson, T., Shinkle, M., & Kletzel, M. (2011). Busulfan dosing in children with BMIs ≥ 85% undergoing HSCT: a new optimal strategy. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 17(9), 1383-8. https://doi.org/10.1016/j.bbmt.2011.01.013
Browning B, et al. Busulfan Dosing in Children With BMIs ≥ 85% Undergoing HSCT: a New Optimal Strategy. Biol Blood Marrow Transplant. 2011;17(9):1383-8. PubMed PMID: 21288495.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Busulfan dosing in children with BMIs ≥ 85% undergoing HSCT: a new optimal strategy. AU - Browning,Brittan, AU - Thormann,Kimberly, AU - Donaldson,Amy, AU - Halverson,Terri, AU - Shinkle,Marie, AU - Kletzel,Morris, Y1 - 2011/02/01/ PY - 2010/07/22/received PY - 2011/01/20/accepted PY - 2011/2/4/entrez PY - 2011/2/4/pubmed PY - 2012/2/18/medline SP - 1383 EP - 8 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 17 IS - 9 N2 - Childhood obesity has more than tripled in the past 30 years. The prevalence of overweight and obese children has also increased in the pediatric cancer setting, causing substantial concern over proper chemotherapeutic dosing in this population. The purpose of this study was to determine if children with an increased body mass index (BMI) have an alteration in busulfan pharmacokinetics during hematopoietic stem cell transplant (HSCT) conditioning. We retrospectively reviewed data on busulfan pharmacokinetics (PK) on HSCT subjects (subjects were part of a prospective study previously reported by our group at Children's Memorial Hospital) to determine appropriateness of dosing. Subjects were divided into appropriate BMI categories (<25th percentile, 25th-85th percentile, ≥ 85th percentile) and busulfan PK dosing was analyzed (test dose, regimen dose, area under the curve [AUC], and clearance). The dosing based on PK test dose data of children with BMI ≥ 85% was compared against the package insert dosing recommendations of using adjusted ideal body weight (AIBW) in obese patients to determine which dosing schema was most accurate. Children with high BMIs had higher AUCs when dosing on actual weight then their normal or low BMI counterparts. This indicates that children with a high BMI require less drug (2.9 mg/kg using actual body weight) to achieve the same AUC as children with normal BMI (4.0 mg/kg) or low BMI (3.6 mg/kg). Using the recommended AIBW dosing schema, 53% of the patients with high BMIs would have had regimen dose AUCs ≥ 20% over/under the target; whereas with the PK test dose method, only 16% of the patients with high BMIs had regimen dose AUCs ≥ 20% over/under the target. PK testing continues to be the gold standard for busulfan dosing in children. Particular vigilance should be paid to PK monitoring in high BMI categories because of the potential risk of imprecise dosing when using the AIBW schema. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/21288495/Busulfan_dosing_in_children_with_BMIs_≥_85_undergoing_HSCT:_a_new_optimal_strategy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(11)00075-9 DB - PRIME DP - Unbound Medicine ER -