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Safety, efficacy, and pharmacokinetics of intravenous busulfan in children undergoing allogeneic hematopoietic stem cell transplantation.
Pediatr Blood Cancer. 2010 Feb; 54(2):291-8.PB

Abstract

PURPOSE

To determine the safety, efficacy, and PK profile of intravenous busulfan (Bu) in the context of a Bu and cyclophosphamide (IVBuCy) preparative regimen in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

METHODS

Twenty-four children were enrolled in an open-label, multicenter trial of IVBuCy as the preparative regimen for HLA-matched sibling allogeneic HSCT. IVBu was administered q6 hr for 16 doses with a targeted area under the curve (AUC) of 900-1,350 microMol-min. The initial dose was 0.8 mg/kg for children >4 years of age and 1 mg/kg for those <4 years of age. PK of the first dose IVBu was determined to calculate a single dosage adjustment, and with the 9th and 13th doses to confirm steady-state PK.

RESULTS

The targeted AUC was achieved with the first dose in 17/24 (71%) of the children using the age-adjusted dosing approach. Dosing was increased in five patients, and reduced in two patients to achieve target values. After dose adjustment based on PK, 91% of the children had an AUC within the target range at steady state (AUCss). Median final dosing and clearance (CL) of IVBu were 1.1 mg/kg and 4.1 ml/min/kg in patients < or =4 years, and 0.9 mg/kg and 2.9 ml/min/kg in patients >4 years. All children were engrafted with documented donor chimerism. No late rejections or graft failures occurred. Four patients had veno-occlusive disease, three of which resolved within 2 weeks of onset. Two children died from transplant-related causes unrelated to Bu.

CONCLUSION

IVBu is a safe and effective and offers the benefit of predictable and consistent systemic exposure.

Authors+Show Affiliations

Cardinal Glennon Children's Hospital/Saint Louis University, St. Louis, Missouri, USA. donna.wall@cancercare.mb.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19743300

Citation

Wall, Donna A., et al. "Safety, Efficacy, and Pharmacokinetics of Intravenous Busulfan in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation." Pediatric Blood & Cancer, vol. 54, no. 2, 2010, pp. 291-8.
Wall DA, Chan KW, Nieder ML, et al. Safety, efficacy, and pharmacokinetics of intravenous busulfan in children undergoing allogeneic hematopoietic stem cell transplantation. Pediatr Blood Cancer. 2010;54(2):291-8.
Wall, D. A., Chan, K. W., Nieder, M. L., Hayashi, R. J., Yeager, A. M., Kadota, R., Przepiorka, D., Mezzi, K., & Kletzel, M. (2010). Safety, efficacy, and pharmacokinetics of intravenous busulfan in children undergoing allogeneic hematopoietic stem cell transplantation. Pediatric Blood & Cancer, 54(2), 291-8. https://doi.org/10.1002/pbc.22227
Wall DA, et al. Safety, Efficacy, and Pharmacokinetics of Intravenous Busulfan in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation. Pediatr Blood Cancer. 2010;54(2):291-8. PubMed PMID: 19743300.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety, efficacy, and pharmacokinetics of intravenous busulfan in children undergoing allogeneic hematopoietic stem cell transplantation. AU - Wall,Donna A, AU - Chan,Ka Wah, AU - Nieder,Michael L, AU - Hayashi,Robert J, AU - Yeager,Andrew M, AU - Kadota,Richard, AU - Przepiorka,Donna, AU - Mezzi,Khaled, AU - Kletzel,Morris, AU - ,, PY - 2009/9/11/entrez PY - 2009/9/11/pubmed PY - 2010/1/27/medline SP - 291 EP - 8 JF - Pediatric blood & cancer JO - Pediatr Blood Cancer VL - 54 IS - 2 N2 - PURPOSE: To determine the safety, efficacy, and PK profile of intravenous busulfan (Bu) in the context of a Bu and cyclophosphamide (IVBuCy) preparative regimen in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Twenty-four children were enrolled in an open-label, multicenter trial of IVBuCy as the preparative regimen for HLA-matched sibling allogeneic HSCT. IVBu was administered q6 hr for 16 doses with a targeted area under the curve (AUC) of 900-1,350 microMol-min. The initial dose was 0.8 mg/kg for children >4 years of age and 1 mg/kg for those <4 years of age. PK of the first dose IVBu was determined to calculate a single dosage adjustment, and with the 9th and 13th doses to confirm steady-state PK. RESULTS: The targeted AUC was achieved with the first dose in 17/24 (71%) of the children using the age-adjusted dosing approach. Dosing was increased in five patients, and reduced in two patients to achieve target values. After dose adjustment based on PK, 91% of the children had an AUC within the target range at steady state (AUCss). Median final dosing and clearance (CL) of IVBu were 1.1 mg/kg and 4.1 ml/min/kg in patients < or =4 years, and 0.9 mg/kg and 2.9 ml/min/kg in patients >4 years. All children were engrafted with documented donor chimerism. No late rejections or graft failures occurred. Four patients had veno-occlusive disease, three of which resolved within 2 weeks of onset. Two children died from transplant-related causes unrelated to Bu. CONCLUSION: IVBu is a safe and effective and offers the benefit of predictable and consistent systemic exposure. SN - 1545-5017 UR - https://www.unboundmedicine.com/medline/citation/19743300/Safety_efficacy_and_pharmacokinetics_of_intravenous_busulfan_in_children_undergoing_allogeneic_hematopoietic_stem_cell_transplantation_ L2 - https://doi.org/10.1002/pbc.22227 DB - PRIME DP - Unbound Medicine ER -