December 11, 2011

Ben Leach

Study finds that peripheral blood stem cell (PBSC) transplants increase the incidence of graft-versus-host disease (GVHD).

A new study has found that peripheral blood stem cell (PBSC) transplants from unrelated donors increase the incidence of graft-versus-host disease (GVHD), thereby putting into question the validity of using a form of transplantation that had previously been shown to be clinically beneficial.

The phase III, prospective, randomized, multicenter trial, which was presented at the 53rd Annual Meeting of the American Society of Hematology, held in San Diego, California, found that 53% of patients receiving PBSC transplants experienced overall chronic GVHD, compared to 40% of patients who had received bone marrow transplants (P=0.02). The study also found that 46% of patients had chronic extensive GVHD, compared to 31% of patients who received bone marrow stem cells.

Peripheral blood stem cells are stem cells that are found in bone marrow, which have been moved into the bloodstream through a special regimen such as apheresis, which collects PBSCs through a tube inserted into the vein. This method has been used more frequently in the transplant setting, because about 70% of patients receiving transplants who cannot find a donor within their family are able to find an unrelated donor who can supply them with PBSCs. Previous studies that examined patients who received PBSCs from related donors showed that patients had better engraftment after the transplant, lower relapse rates, and increased survival rates compared to patients who had received bone marrow transplants. However, those trials also showed an increased incidence in GVHD.

Claudio Anasetti, MD, chair of the department of Blood and Marrow Transplant at H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida and lead author of the study, said that there has been a 75% increased use of PBSCs from unrelated donors without any appropriate study. Researchers from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) conducted the trial to compare 2-year survival probabilities in patients who had received PBSC transplants or bone marrow transplants. Patients were randomized to receive bone marrow transplants (n=278) or PBSCs (n=273) as the graft source.

While the trial found no differences in overall survival, relapse, nonrelapse mortality, or acute GVHD between patients who had received these grafts from unrelated donors, the differences in GVHD proved to be a major point of concern.

"The increase was significant," said Anasetti at the meeting. "Why would anyone want to have a 16% increase of living with graft-versus-host disease?"

Graft-versus-host disease often results from slight differences between the cells of the donor and the recipient, which cause T-cells from the newly transplanted organ to attack the recipient's body. Chronic GVHD can be managed by immunosuppressive drugs, which can lower the body's ability to fight infection. The National Institutes of Health estimate that between 30% and 40% of patients who receive a donated organ from a related donor experience GVHD, while 60% to 80% of patients who receive an organ from an unrelated donor experience the disease.

Anasetti said that the results of this trial will, most likely, cause many transplant physicians to rethink treatment strategies for patients, including whether or not bone marrow transplants are a more appropriate method for patients with various forms of blood cancer. However, Anasetti said PBSCs may still be a treatment option despite the trial, because bone marrow transplants are less likely to achieve engraftment.

"More effective strategies to prevent graft-versus-host disease are needed to improve outcomes for all patients receiving unrelated donor transplants," Anasetti said.