Optimizing Stem Cell Transplant for Cancer

优化癌症干细胞移植

• 批准号: 7075292
• 负责人: Pamala A Jacobson
• 金额: $ 12.73万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-14 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7075292
• 关键词: clinical research; dosage; graft versus host disease; hematopoietic tissue transplantation; human subject; mycophenolate mofetil; patient oriented research; pharmacokinetics; stem cell transplantation; transplantation immunology

DESCRIPTION (provided by applicant): Pamala Jacobson, Pharm.D. is an Assistant Professor in the Department of Experimental and Clinical Pharmacology at the University of Minnesota (MN). She has 9 years of clinical experience in hematopoietic stem cell transplantation (HSCT) and now wishes to change her career focus to clinical research. Her long-termcareer goal is to become an independent investigator focusing on clinical pharmacology in HSCT. Her immediate goal is, to receive research training to prepare herself as an independently funded investigator. She proposes to conduct mentored clinical research under her mentors and complete the Clinical Research Masters Program, University of MN, The University of MN is home to one of the oldest and largest academically based HSCT programs in the world, a top-ranked College of Pharmacy and School of Public Health, and is well equipped to support the candidate. The program of study will focus on clinical trial design, biostatistics, ethics, pharmacokinetics and pharmacodynamics. The applicant's research will explore the pharmacokinetics of the immunosuppressant, mycophenolate, and the relationships between pharmacokinetics and clinical outcomes in nonmyeloablative allogeneic HSCT. Less toxic "nonmyeloablative" preparative regimens, containing mycophenolate, are under investigation. These regimens use a standard, fixed dose of mycophenolate and are associated with variable immunosuppression and outcomes. We hypothesize that the variability in outcomes is related to differences in mycophenolate pharmacokinetics. Specific Aim I will evaluate the relationships between mycophenolate pharmacokinetic measures and clinical endpoints. Specific Aim II will assess pretransplant mycophenolate pharmacokinetics to determine inter-patient variability and identify covariates associated with their variability. Specific Aim III will assess posttransplant pharmacokinetics to determine intra-patient variability and identify peritransplant events associated with variability. We anticipate that monitoring of mycophenolate concentrations and individualized dosing is warranted. The long-term goal of this research is to reduce the rates of graft vs. host disease, graft failure, toxicity and improve survival following nonmyeloablative HSCT. The overall goal is to provide the applicant with formal and comprehensive training as a clinical cancer investigator.

描述（由申请人提供）：Pamala Jacobson，Pharm.D.是明尼苏达大学（MN）实验和临床药理学系的助理教授。 她在造血干细胞移植（HSCT）方面有9年的临床经验，现在希望将她的职业重点转向临床研究。她的长期职业目标是成为一名专注于HSCT临床药理学的独立研究者。 她的直接目标是，接受研究培训，准备自己作为一个独立资助的调查员。 她建议在她的导师指导下进行临床研究，并完成临床研究硕士课程，明尼苏达大学，明尼苏达大学是世界上最古老，最大的学术HSCT项目之一，排名第一的药学院和公共卫生学院，并配备齐全，以支持候选人。 研究计划将侧重于临床试验设计，生物统计学，伦理学，药代动力学和药效学。 申请人的研究将探索免疫抑制剂霉酚酸酯的药代动力学，以及非清髓性异基因HSCT中药代动力学与临床结局之间的关系。 含有霉酚酸酯的毒性较低的“非清髓性”准备方案正在研究中。 这些方案使用标准、固定剂量的霉酚酸酯，并与可变的免疫抑制和结局相关。 我们推测，结果的变异性与霉酚酸酯药代动力学的差异有关。 具体目的我将评价霉酚酸酯药代动力学指标和临床终点之间的关系。 Specific Aim II将评估移植前麦考酚酯的药代动力学，以确定患者间的变异性，并确定与其变异性相关的协变量。 Specific Aim III将评估移植后药代动力学，以确定患者内变异性并识别与变异性相关的移植围手术期事件。 我们预计，监测麦考酚酯浓度和个体化给药是必要的。 本研究的长期目标是降低非清髓性HSCT后移植物抗宿主病、移植物衰竭、毒性的发生率，提高生存率。 总体目标是为申请人提供作为临床癌症研究者的正式和全面的培训。

项目成果

Effect of aprepitant on intravenous tacrolimus disposition in reduced intensity hematopoietic stem cell transplantation.

• DOI: 10.1177/1078155208089846
• 发表时间: 2008-09-01
• 期刊: Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners
• 作者: Ibrahim, Rami B;Abidi, Muneer H;Edwards, David J
• 通讯作者: Edwards, David J

Comparison of two mycophenolate mofetil dosing regimens after hematopoietic cell transplantation.

• DOI: 10.1038/bmt.2008.428
• 发表时间: 2009-07
• 期刊: BONE MARROW TRANSPLANTATION
• 影响因子: 4.8
• 作者: Jacobson, P.;El-Massah, S. F.;Rogosheske, J.;Kerr, A.;Long-Boyle, J.;DeFor, T.;Jennissen, C.;Brunstein, C.;Wagner, J.;Tomblyn, M.;Weisdorf, D.
• 通讯作者: Weisdorf, D.

Obesity effects on cyclophosphamide-induced DNA damage in hematopoietic cell transplant recipients.

肥胖对造血细胞移植受者环磷酰胺诱导的 DNA 损伤的影响。

• 发表时间: 2012
• 期刊: In vivo (Athens, Greece)
• 作者: Johnson,L'AurelleA;Tretyakova,Natalia;Jacobson,PamalaA
• 通讯作者: Jacobson,PamalaA

High unbound mycophenolic acid concentrations in a hematopoietic cell transplantation patient with sepsis and renal and hepatic dysfunction.

患有败血症和肝肾功能障碍的造血细胞移植患者体内未结合的霉酚酸浓度较高。

• DOI: 10.1016/j.bbmt.2005.08.037
• 发表时间: 2005
• 期刊: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
• 作者: Jacobson,Pamala;Long,Janel;Rogosheske,John;Brunstein,Claudio;Weisdorf,Daniel
• 通讯作者: Weisdorf,Daniel