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Oral busulfan pharmacokinetics and engraftment in children with Hurler syndrome and other inherited metabolic storage diseases undergoing hematopoietic cell transplantation.
Bone Marrow Transplant. 2001 Apr; 27(8):855-61.BM

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is the only treatment for selected inherited metabolic storage diseases (IMSD); a significant shortcoming is failure to achieve donor-derived engraftment. This study was undertaken to determine whether busulfan pharmacokinetics (BU PK) are altered in children with IMSD and whether BU concentrations are important in achieving engraftment. BU samples were obtained from 39 IMSD children, including 20 children with Hurler syndrome, undergoing HCT. Patients received oral BU (40 mg/m(2)/dose x 8 doses), cyclophosphamide (60 mg/kg/day x 2 doses) and TBI (750 cGy in one fraction) as a preparative regimen. Median (range) oral clearance corrected for bioavailability (Cl/F in ml/min/kg), area under the curve (AUC in ng min/ml) and BU plasma concentration (Cp in ng/ml) with the fourth dose were 5.2 (2.1-11.4), 318 294 (112 893-640 995) and 950 (314-1780), respectively. Children < 3 years of age had lower AUC and Cp but higher Cl/F (P < or = 0.03). BU Cp (P = 0.06) or marrow cell dose (P = 0.32) was not different in Hurler syndrome compared to other IMSD. A median BU Cp of 959 and 831 ng/ml was achieved in children with full and failed early engraftment, respectively. There was no difference in early and late engraftment between children with Hurler and other IMSD. In conclusion, we found no significant association between engraftment, marrow cell dose and BU exposure when combined with CY and TBI in children with IMSD.

Authors+Show Affiliations

Jacobson P
Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
Park JJ
No affiliation info available
DeFor TE
No affiliation info available
Thrall M
No affiliation info available
Abel S
No affiliation info available
Krivit W
No affiliation info available
Peters C
No affiliation info available

MeSH

Administration, OralAdolescentAdultArea Under CurveBusulfanChildChild, PreschoolCombined Modality TherapyFemaleGraft SurvivalHematopoietic Stem Cell TransplantationHumansInfantLysosomal Storage DiseasesMaleMetabolic Clearance RateMucopolysaccharidosis ISurvival RateTransplantation ConditioningTransplantation, HomologousVascular Diseases

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11477444

Citation

Jacobson, P, et al. "Oral Busulfan Pharmacokinetics and Engraftment in Children With Hurler Syndrome and Other Inherited Metabolic Storage Diseases Undergoing Hematopoietic Cell Transplantation." Bone Marrow Transplantation, vol. 27, no. 8, 2001, pp. 855-61.
Jacobson P, Park JJ, DeFor TE, et al. Oral busulfan pharmacokinetics and engraftment in children with Hurler syndrome and other inherited metabolic storage diseases undergoing hematopoietic cell transplantation. Bone Marrow Transplant. 2001;27(8):855-61.
Jacobson, P., Park, J. J., DeFor, T. E., Thrall, M., Abel, S., Krivit, W., & Peters, C. (2001). Oral busulfan pharmacokinetics and engraftment in children with Hurler syndrome and other inherited metabolic storage diseases undergoing hematopoietic cell transplantation. Bone Marrow Transplantation, 27(8), 855-61.
Jacobson P, et al. Oral Busulfan Pharmacokinetics and Engraftment in Children With Hurler Syndrome and Other Inherited Metabolic Storage Diseases Undergoing Hematopoietic Cell Transplantation. Bone Marrow Transplant. 2001;27(8):855-61. PubMed PMID: 11477444.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral busulfan pharmacokinetics and engraftment in children with Hurler syndrome and other inherited metabolic storage diseases undergoing hematopoietic cell transplantation. AU - Jacobson,P, AU - Park,J J, AU - DeFor,T E, AU - Thrall,M, AU - Abel,S, AU - Krivit,W, AU - Peters,C, PY - 2000/11/30/received PY - 2001/01/02/accepted PY - 2001/7/31/pubmed PY - 2002/1/11/medline PY - 2001/7/31/entrez SP - 855 EP - 61 JF - Bone marrow transplantation JO - Bone Marrow Transplant VL - 27 IS - 8 N2 - Allogeneic hematopoietic cell transplantation (HCT) is the only treatment for selected inherited metabolic storage diseases (IMSD); a significant shortcoming is failure to achieve donor-derived engraftment. This study was undertaken to determine whether busulfan pharmacokinetics (BU PK) are altered in children with IMSD and whether BU concentrations are important in achieving engraftment. BU samples were obtained from 39 IMSD children, including 20 children with Hurler syndrome, undergoing HCT. Patients received oral BU (40 mg/m(2)/dose x 8 doses), cyclophosphamide (60 mg/kg/day x 2 doses) and TBI (750 cGy in one fraction) as a preparative regimen. Median (range) oral clearance corrected for bioavailability (Cl/F in ml/min/kg), area under the curve (AUC in ng min/ml) and BU plasma concentration (Cp in ng/ml) with the fourth dose were 5.2 (2.1-11.4), 318 294 (112 893-640 995) and 950 (314-1780), respectively. Children < 3 years of age had lower AUC and Cp but higher Cl/F (P < or = 0.03). BU Cp (P = 0.06) or marrow cell dose (P = 0.32) was not different in Hurler syndrome compared to other IMSD. A median BU Cp of 959 and 831 ng/ml was achieved in children with full and failed early engraftment, respectively. There was no difference in early and late engraftment between children with Hurler and other IMSD. In conclusion, we found no significant association between engraftment, marrow cell dose and BU exposure when combined with CY and TBI in children with IMSD. SN - 0268-3369 UR - https://www.unboundmedicine.com/medline/citation/11477444/Oral_busulfan_pharmacokinetics_and_engraftment_in_children_with_Hurler_syndrome_and_other_inherited_metabolic_storage_diseases_undergoing_hematopoietic_cell_transplantation_ L2 - https://doi.org/10.1038/sj.bmt.1703010 DB - PRIME DP - Unbound Medicine ER -
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