A5059738858- Hematopoietic Stem Cell Transplantation
- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Renal Transplantation Outcomes and Treatments
- Cancer Treatment and Pharmacology
- Estrogen and related hormone effects
- Pharmacogenetics and Drug Metabolism
- Cancer therapeutics and mechanisms
- Chemotherapy-induced organ toxicity mitigation
- Chronic Lymphocytic Leukemia Research
- Childhood Cancer Survivors' Quality of Life
- Chronic Myeloid Leukemia Treatments
- Head and Neck Cancer Studies
- Metal complexes synthesis and properties
- Synthesis and Characterization of Heterocyclic Compounds
- Liver Disease and Transplantation
- Retinoids in leukemia and cellular processes
- Pharmacology and Obesity Treatment
- Ferrocene Chemistry and Applications
- Hemoglobinopathies and Related Disorders
- Pharmaceutical studies and practices
- Radiopharmaceutical Chemistry and Applications
- Drug Transport and Resistance Mechanisms
- Nanoparticle-Based Drug Delivery
- Hormonal and reproductive studies
Foothills Medical Centre
2011-2024
University of Calgary
2004-2023
Alberta Health Services
2013-2019
BC Cancer Agency
2006
Low plasma busulfan (Bu) area under the concentration-time curve (AUC) is associated with graft failure and relapsed leukemias, high AUC toxicities when Bu used orally or i.v. 4 times daily combined cyclophosphamide in myeloablative hematopoietic stem cell transplantation (SCT) conditioning regimens. We report its association clinical outcomes 130 patients hematologic malignancies given a once-daily (3.2 mg/kg days -5 to -2) fludarabine (Flu, 50 mg/m(2) -6 regimen. Total-body irradiation...
A combination of fludarabine (Flu) and daily i.v. busulfan (Bu) is well tolerated effective in patients undergoing allogeneic hematopoietic stem cell transplantation. Although there some evidence that Bu exposures exceeding 6000 μM.min [corrected] may lead to excessive toxicity, little information on the effect below this level outcomes. We studied exposure, as measured by area under concentration-time curve (AUC), 158 with various hematologic malignancies an attempt identify optimal range...
Intravenous (i.v.) busulfan (Bu) administered once daily in myeloablative transplant regimens is convenient, effective, and relatively well tolerated. Therapeutic drug monitoring recommended as nonrelapse mortality increases when exposure, determined by the area under plasma concentration versus time curve (AUC), exceeds 6000 μM·min. We describe sequential studies to achieve accurate prediction of treatment doses Bu based on kinetics a smaller test dose. A total 335 patients with hematologic...
A physiologically based pharmacokinetic (PBPK) model of the DNA-alkylating agent busulfan was slightly modified and scaled from adults to children in order predict systemic drug exposure children. Capitalizing on recent major software release PK-Sim®, we refined our PBPK by implementing glutathione S transferase (GST) 11 organs using integrated enzyme expression database. In addition, two irreversible binding processes (i.e., DNA plasma protein binding) were applied Koff KD values. The...
Antithymocyte globulin (ATG) levels and clearance vary significantly among patients receiving the same weight-based dose of ATG. To date, ATG area under curve (AUC), its determinants, impact on clinical outcomes have been examined in pediatric hematopoietic cell transplant (HCT) adult nonmyeloablative HCT. Here we set out to examine AUC 219 uniformly treated adults undergoing myeloablative allogeneic HCT at our institution. Sera were collected for determination pre- or post-HCT AUC. The...
Abstract It remains unknown why rabbit antithymocyte globulin (ATG; Thymoglobulin) has not affected relapse after hematopoietic cell transplantation (HCT) in randomized studies. We hypothesized that high pre-HCT ATG area under the curve (AUC) would be associated with a low incidence of relapse, whereas post-HCT AUC relapse. measured serum levels capable binding to mononuclear cells (MNCs), lymphocytes, T cells, CD4 or CD33 cells. estimated pre- and AUCs 152 adult recipients myeloablative...
Tamoxifen is a key therapeutic option for breast cancer treatment. Understanding its complex metabolism and pharmacokinetics important dose optimization. We examined the possibility of utilizing archival formalin-fixed paraffin-embedded (FFPE) tissue as an alternative sample source quantification since well-annotated retrospective samples were always limited. Six 15 μm sections FFPE tissues deparaffinized with xylene purified using solid-phase extraction. metabolites separated detected by...
Abstract Background Hematopoietic stem cell transplantation can be curative for children with difficult‐to‐treat leukemia. The conditioning regimen utilized is known to influence outcomes. We report outcomes of the used at Alberta Children's Hospital, consisting busulfan (with pharmacokinetic target 3750 μmol*min/L/day ±10%) 4 days, higher dose (250 mg/m 2 ) fludarabine and 400 centigray (cGy) total body irradiation. Procedure This retrospective study involved receiving transplant acute...
1524 Background: The clinical impact of CYP2D6 genetic polymorphisms on tamoxifen (Tam) remains unclear. Active metabolite levels Tam can be influenced by drug interaction and compliance. This study evaluated the association steady state plasma its metabolites with outcomes in samples collected MA.12. Premenopausal women (n=672) high risk node negative positive breast cancer following adjuvant chemotherapy were randomized to or placebo. There was an improvement DFS (HR 0.77; p=0.056) but not...
Background Hematopoietic stem cell transplantation can be curative for children with difficult to treat leukemia. The conditioning regimen utilised is known influence outcomes. We report outcomes of the used at Alberta Children’s Hospital, consisting busulfan (with pharmacokinetic target 3750μmol*min/day +/-10%) 4 days, higher dose (250 mg/m2) fludarabine and 400 centigray total body irradiation. Procedure This retrospective study involved receiving transplant acute lymphoblastic leukemia...
15523 Background: Docetaxel and cisplatin are both active agents in the treatment of advanced SCCHN. In phase II trials combination docetaxel delivered on a 3 weekly schedule recurrent/metastatic SCCHN demonstrated response rates (RR) 33–46%, however it is associated with significant morbidities related mortalities. IB trial design we sought to determine maximal tolerated dose (MTD) recommended for further study trial. Methods: Patients measurable locoregionally recurrent and/or metastatic...