Optimizing Stem Cell Transplant for Cancer

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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.