Researcher refining matching factors for bone marrow

A patient requiring bone marrow transplantation due to chronic myeloid leukemia, a cancer of the blood cells, stands his or her best chance if the donor is a sibling. Siblings will genetically match more closely than other family members. The closer the match, the less chance the patient’s body will reject the transplanted cells, or that graft-versus-host disease will develop.

Effie Petersdorf

Yet, the chance that any given siblings will be genotypically matched is only 25 percent. What happens, then, if a suitably matched related donor can’t be found? The answer, says Dr. Effie Petersdorf, is to broaden the search to the entire human population.

Petersdorf, a UW associate professor of medicine based at the Fred Hutchinson Cancer Research Center, studies how to match unrelated donors and recipients more precisely, as well as the significance of specific matches, with the goal of improving outcomes for patients. And, ultimately, she is improving the odds.

Petersdorf will discuss her research in a Science in Medicine Lecture, titled “Genomics of Hematopoietic Cell Transplantation,” from noon to 1 p.m. on Thursday, Feb. 24 in room T-625, Health Sciences Center.

The genes Petersdorf studies are called the human leukocyte antigen (HLA) genes, which are responsible for determining our tissue type: the HLA-A, -B, -C, -DR, -DQ, and -DP antigens. These antigens are believed to be responsible for triggering an immune response that destroys transplanted marrow cells, as well as being involved in graft-versus-host disease (GVHD) in which the donor’s transplanted cells attack the patient’s organs and tissues.

In a study of 300 patients who underwent unrelated donor marrow transplantation between 1985 and 1998, Petersdorf and her colleagues, notably Drs. John Hansen, Claudio Anasetti and Paul Martin of the Hutch’s Program in Human Immunogenetics, determined that recipients whose HLA-A, -B, -C, -DRB1, and -DQB1 genes matched the donor’s had a significantly better chance of surviving than those patients whose genes did not match. The study also proved that mismatches in HLA-A, -B and -C genes result in graft failure, while mismatches in the -DR, -DQ genes result in GVHD.

As matching the genes of donors and recipients becomes more and more accurate, more lives will be saved with marrow transplantation.

Further studies are needed. The HLA genes are located in the major histocompatibility complex (MHC), a region on chromosome 6 essential to the immune system. Several new genes have been mapped within the HLA region. HLA mismatches between unrelated donors and recipients are inevitable, but perhaps not all mismatches are clinically significant, Petersdorf suggests.

“We know we should match for as many of the HLA genes as possible, but a total match is feasible for only a minority of patients, so we need to know which mismatches are well-tolerated and which are not,” she said.

Petersdorf was one of 60 young scientists to receive the Presidential Early Career Award for Scientists and Engineers last year. The awards are the highest bestowed by the United States government on young investigators. She received an M.D. in 1982 from McGill University School of Medicine and completed an internship, residency and fellowship here at the UW. Petersdorf joined the faculty in 1988. ¶

Will Morton