The Frederick National Laboratory for Cancer Research has entered into a new partnership with Fred Hutchinson Cancer Research Center that if successful, could improve current methods of donor selection and thereby make lifesaving transplant procedures more readily available for patients with leukemia, multiple myeloma, and other disorders.
For patients with blood disorders such as leukemia and multiple myeloma, transplantation can be a lifesaving treatment. The procedure requires compatible donors, because serious post-transplant complications can occur, including life-threatening graft-versus-host disease, which occurs when transplanted immune cells attack healthy tissues.
The current procedure for determining compatibility relies on human leukocyte antigen (HLA) matching, a method to determine how closely the tissues of one person match another person. However, matched stem cell sources are not always available, particularly for unrelated donor-recipient pairs, and there are no criteria for selecting the least risky mismatched donor.
To help improve donor selection and increase the availability of lifesaving transplantations to more patients, the Frederick National Lab and Fred Hutch have signed a contractor Cooperative Research and Development Agreement (cCRADA) to jointly conduct research exploring the role of HLA expression in defining permissible HLA mismatches. This collaboration brings together two research teams with significant experience studying HLA gene expression and its role in stem cell transplantation.
The use of HLA expression is a novel approach for optimizing donor selection. As the global transplant experience has matured, patient–donor ethnicity has been recognized as an important determinant of post-transplant outcomes. Frederick National Lab and Fred Hutch investigators have previously conducted research showing that diversity in the Major Histocompatibility Complex (a set of cell surface proteins that determine tissue compatibility) and Killer Immune Receptor (KIR) genetic regions (which regulate cell growth) are important for patient outcomes for HLA matched and mismatched transplantations.
Through the cCRADA, the Frederick National Lab and Fred Hutch will examine the underlying mechanisms of these genotype associations with transplant outcomes. They will examine large, ethnically diverse transplant populations to study single nucleotide polymorphisms (variations in a single nucleotide), the role of expression and specificity of KIR-HLA interactions, and how allotype (variants of gene) interactions affect outcomes. Based on this research, the team will rank the immunogenetic factors that most strongly predict survival. This ranking can be directly translated to clinical practice to help overcome existing roadblocks in alternative donor transplantation.
By Victoria Brun, science writer, Partnership Development Office
Image: Human cells with leukemia. Photo courtesy National Cancer Institute.