Fred Hutchinson Cancer Research Center has entered into a new partnership with the National Cancer Institute-sponsored Frederick National Laboratory for Cancer Research that aims to increase access to lifesaving stem-cell transplants for those without a tissue-matched, related donor. If successful, the collaboration could improve current methods of donor selection and make stem-cell transplants more readily available for those with leukemia, multiple myeloma and other blood disorders.

For such patients, transplantation can be a lifesaving treatment, but it requires the availability of compatible stem-cell donors. Otherwise, serious post-transplant complications can arise, including the potentially deadly graft-vs-host disease, or GVHD, which occurs when transplanted immune cells attack the recipient’s healthy tissues.

The partnership is co-led by Fred Hutch clinical researcher Dr. Effie Wang Petersdorf and Dr. Mary Carrington, director of the Basic Science Program at Frederick; both specialize in studying the genes that influence tissue matching between donors and transplant recipients. Specifically, they are interested in studying genes that can influence the risk of GVHD.

The current method for determining donor/recipient compatibility relies on human leukocyte antigen, or HLA, matching to tell how closely the tissues of one person match the other. 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 the donor-selection process and increase the availability of transplants for more patients, Fred Hutch and Frederick National Laboratory have signed a contractor Cooperative Research and Development Agreement, or cCRADA, to jointly conduct research exploring the role of HLA expression in defining permissible HLA mismatches.

The use of HLA expression is a novel approach for optimizing donor selection, Petersdorf said. “With the availability of laboratory methods that permit long-range definition of sequence variation across an HLA gene, it is now feasible to identify variants in the regulatory regions of HLA genes that influence HLA expression,” she said.

Petersdorf and colleagues at Frederick previously found that diversity within the major histocompatibility complex region is important for patient outcomes for both HLA-matched and HLA-mismatched transplants.

Through their collaboration, Petersdorf, Carrington and colleagues will examine large, ethnically diverse transplant populations to study such genetic factors that affect patient outcomes. They then will rank immunogenetic factors that most strongly predict survival to help guide optimal donor selection.

“We are entering into an exciting phase of immunogenetics research, where information on gene expression may positively impact our approach to the selection of transplant donors,” Petersdorf said. “Not only is it important to know what kinds of HLA proteins the patient and transplant donor have, and how those proteins differ from one another, but we now appreciate that the amount of HLA protein expressed is also clinically relevant.”

— Adapted from a Frederick National Laboratory for Cancer Research news release