Together with 16 other institutions in the United States, University ofMinnesota researchers led the largest study to date in patients withleukemia and related disorders undergoing bone marrow transplantationfrom unrelated donors. The study was designed to determine whether oneof two general approaches to prevent graft-versus-host-disease (GVHD),a potentially lethal complication, might result in improved survival.
While the trial demonstrated similar survival rates, the study was themost comprehensive to date, evaluating various clinical outcomes,resource utilization, costs, and health quality of life. The study,published in the Aug. 3, 2005 online issue of The Lancet, will likelyserve as the benchmark for all future studies in this patientpopulation.
Graft-versus-host-disease is a common complication after bone marrowtransplantation in which the immune cells from the donated marrowattack the body of the patient who received the transplant. Severityranges from mild to life threatening, and the disease and its treatmentcan have a profound effect on quality of life.
The two primary strategies for preventing GVHD, the removal of T-cells(the cell that causes GVHD) and immunosuppressive drug therapy(suppression of T-cell function), were studied in this trial. While theprimary aim of the study was to demonstrate whether one approach mightbe better than the other in terms of disease-free survival three yearsafter transplantation, the study also systematically compared theincidence of various complications (GVHD, graft failure,therapy-related side effects, disease recurrence) as well asutilization of blood products, nutritional supplementation, number ofadmissions to the hospital and intensive care unit, hospital costs, andhealth quality of life.
"While the T-cell depletion approach was very effective in reducing therisk of GVHD, a higher risk of viral infection in general and higherrisk of disease recurrence specifically in patients with chronicmyelogenous leukemia, eliminated the potential benefit of reducedGVHD," ," said John E. Wagner, M.D., professor of pediatrics andscientific director of clinical research, Blood and MarrowTransplantation Program and Stem Cell Institute, and lead author of thestudy. "Overall, we observed no differences in survival at three yearsand no appreciable differences in cost or quality of life."
These results counter what investigators might have guessed and reflectthe critical importance of performing large randomized trials. "Priorto this study, colleagues promoting T-cell depletion, like myself,predicted that T-cell depletion would have offered a better chance ofsurvival," Wagner said. "What is abundantly clear is that T-celldepletion and GVHD prevention is only one step in figuring out how toimprove upon the chance of cure in unrelated marrow transplantpatients. The next hurdle is to find ways to fix the crippled immunesystem."
Despite the lack of evidence that one approach was better than theother, "the results clearly point out the limitations of bone marrowtransplants," Wagner said. However, he added that the methodologicalapproaches used and study results will be valuable benchmarks forfuture studies of novel treatments for leukemias and otherblood-related cancers.
The study was sponsored by the National Heart, Lung and Blood Institute.
Materials provided by University of Minnesota. Note: Content may be edited for style and length.
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