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Research Abstracts Online
January 2008 - March 2009

University of Minnesota Twin Cities
School of Pharmacy
Department of Experimental and Clinical Pharmacology

PI: Pamala A. Jacobson

Pharmacogenetics of Steroid Resistance in Unrelated and Single-cord Patients Treated for Acute Graft-versus-Host Disease

A number of diseases, such as aplastic anemia, leukemia, lymphoma, sickle-cell disease, myelodysplastic syndrome, neuroblastoma, Ewing’s Sarcoma, and multiple myeloma, utilize treatment with high-dose chemotherapy with or without radiation followed by hematopoietic cell transplantation (HCT). Currently the main sources of hematopoietic cells for transplantation include bone marrow, peripheral blood, or umbilical cord blood from related or unrelated donors. Acute graft-versus-host disease (aGVHD) is one of the most common post-HCT complications where immunocompetent donor T-cells act against recipient tissues with antigens absent from the donor. The primary treatment for aGVHD is high-dose glucocorticoids (GC) leading to immune suppression of activated T-cells. Approximately 50% of individuals treated with GCs are resistant to treatment and are moved to second-line therapies. The primary objective of this retrospective analysis is to determine the association between response to aGVHD therapy with GCs and SNPs involved in the steroid pathway. The target population includes related/unrelated bone marrow, peripheral blood stem cell, or umbilical cord blood tranplant recipients who developed clinically diagnosed aGVHD (grade II-IV) and were treated with prednisone or methylprednisolone as primary therapy. Donor and recipient DNA available in the molecular diagnostics lab is also required for inclusion.

Group Member

Kyle A. Jensen, Graduate Student