SEATTLE - Study demonstrates that marrow transplantation using HLA-matched unrelated donors can be safe and effective therapy for patients with chronic myeloid leukemia (CML) in chronic phase. Seattle researchers also believe that transplantation should not be limited to younger people, under the age of 40 years. Fred Hutchinson Cancer Research Center researchers published the results of their study in the April 2, 1998, issue of The New England Journal of Medicine.
Transplantation has been shown to be the cure for many blood disorders and inherited diseases, including CML. One obstacle has always been the identification of a suitably matched donor. Previously, it was believed that only those CML patients with an HLA-matched sibling donor had an option for curative treatment. This study concludes that marrow transplantation from an HLA-matched unrelated donor can be the treatment of choice for many CML patients and should be considered early in the course of disease to optimize outcome.
According to researchers, this study showed that people diagnosed with CML who undergo an unrelated HLA-matched transplant have a comparable rate of survival to those diagnosed with the same disease who undergo an HLA-matched sibling marrow transplant.
The research team, led by John Hansen, M.D., head of Human Immunogenetics at the Fred Hutchinson Cancer Research Center, reviewed the results of 196 patients transplanted with unrelated donor marrow between May 1985 and December 1994. All patients were under 55 years of age and had been diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. The overall survival rate was 57 percent, but for patients less than 50 years old transplanted from an HLA matched donor within one year from diagnosis the survival rate was 74 percent. The overall survival rate for similar patients who have undergone transplant with a matched sibling donor is 77 percent.
The factors associated with a better survival following an unrelated donor transplant included transplantation within the first year of diagnosis, selection of an HLA-matched donor and post-transplant supportive care aimed at protecting patients from viral and fungal infections.
"These conditions offer the best chance for survival, says Hansen. "The time factor underscores the importance of planning treatment early and performing an HLA family study to determine if the patient has an HLA-matched related donor. If an HLA-matched donor cannot be found within the family, an unrelated donor search should be started."
According to the analysis, graft-versus-host disease (GVHD) still is an issue for patients receiving an unrelated donor transplant, especially if HLA matching is not complete. Researchers believe that GVHD can be minimized in male patients by the use of an HLA-matched male donor, and the risk of chronic GVHD can be minimized in male and female patients by the use of male donors or females who have never given birth.
Previous studies have shown the incidence of graft failure was higher than expected following an unrelated donor transplant for patients with CML. Researchers believe this was a result of undetected HLA incompatibility in the donor. In the current study the marrow was not T-cell depleted (T-cells are the white blood cells that initiate immune responses) and the risk of graft failure was lower than originally anticipated. The patients in this study, however received unmodified marrow grafts replete of donor T cells, whereas the previous studies reporting higher rates of graft failure performed T cell-depletion of donor marrow prior to transplantation.
This study was funded by the National Institutes of Health. The National Marrow Donor Program, and other registries, make it possible for patients to find donors.
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