Largest study of unrelated bone marrow transplantation for leukemia serves as benchmark

08/02/05

Multi-institutional study addresses critical GVHD complication

Together with 16 other institutions in the United States, University of Minnesota researchers led the largest study to date in patients with leukemia and related disorders undergoing bone marrow transplantation from unrelated donors. The study was designed to determine whether one of 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 the most 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 likely serve as the benchmark for all future studies in this patient population.

Graft-versus-host-disease is a common complication after bone marrow transplantation in which the immune cells from the donated marrow attack the body of the patient who received the transplant. Severity ranges from mild to life threatening, and the disease and its treatment can 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 the primary aim of the study was to demonstrate whether one approach might be better than the other in terms of disease-free survival three years after transplantation, the study also systematically compared the incidence of various complications (GVHD, graft failure, therapy-related side effects, disease recurrence) as well as utilization of blood products, nutritional supplementation, number of admissions to the hospital and intensive care unit, hospital costs, and health quality of life.

"While the T-cell depletion approach was very effective in reducing the risk of GVHD, a higher risk of viral infection in general and higher risk of disease recurrence specifically in patients with chronic myelogenous leukemia, eliminated the potential benefit of reduced GVHD," ," said John E. Wagner, M.D., professor of pediatrics and scientific director of clinical research, Blood and Marrow Transplantation Program and Stem Cell Institute, and lead author of the study. "Overall, we observed no differences in survival at three years and no appreciable differences in cost or quality of life."

These results counter what investigators might have guessed and reflect the critical importance of performing large randomized trials. "Prior to this study, colleagues promoting T-cell depletion, like myself, predicted that T-cell depletion would have offered a better chance of survival," Wagner said. "What is abundantly clear is that T-cell depletion and GVHD prevention is only one step in figuring out how to improve upon the chance of cure in unrelated marrow transplant patients. The next hurdle is to find ways to fix the crippled immune system."

Despite the lack of evidence that one approach was better than the other, "the results clearly point out the limitations of bone marrow transplants," Wagner said. However, he added that the methodological approaches used and study results will be valuable benchmarks for future studies of novel treatments for leukemias and other blood-related cancers.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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