New findings in unrelated donor transplants, Parkinson's disease

December 09, 2002

MINNEAPOLIS / ST. PAUL (Dec. 5, 2002)--University of Minnesota researchers will present findings that demonstrate promise for unrelated donor transplant patients and sufferers of Parkinson's disease Monday, Dec. 9, during the American Society of Hematology (ASH) conference in Philadelphia.

The university's Stem Cell Institute director, Catherine Verfaillie, M.D., will receive the 2002 William Dameshek Prize Dec. 10. The prize recognizes outstanding contributions to hematology research.

University researchers presenting new findings at ASH include John Wagner, M.D., Juliet Barker, M.D., Margaret MacMillan, M.D., and Verfaillie. Wagner and Barker will participate in a press conference at 1:30 p.m. EST Monday, December 9.

Wagner's study represents the first large multicenter randomized trial in unrelated bone marrow transplantation evaluating the impact of graft-versus-host disease (GVHD) prophylaxis (treatments to prevent this complication) on three-year disease-free survival in 410 adults and children with leukemia and lymphoma. The study demonstrates that survival is not impacted by the method of GVHD prevention (T cell depletion of the marrow versus immune suppression alone), despite markedly reduced toxicity and GVHD in recipients of T cell-depleted marrow. In both groups, younger patient age and better blood-type match were associated with greater chance of long-term survival. Ongoing quality of life after unrelated transplant is transiently decreased early on but returns to baseline at one year and is similar between treatment groups. This study involved 14 different institutions in the United States and was sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health.

Results from Barker's study support the principle that transplantation of two immunologically distinct (unrelated) umbilical cord blood (UCB) units is not associated with crossed immunological rejection for patients with hematological malignancies (cancers of the blood and bone marrow). Further, it is associated with a high incidence of donor engraftment without an increase in severe acute GVHD. Despite the low cell dose of the predominating unit, donor engraftment may be superior to what would have been predicted based on prior studies of single donor umbilical cord blood transplantation.

MacMillan's research also looks at GVHD and whether there are individual genetic variations in susceptibility to GVHD. Identification of factors that predict the occurrence of severe GVHD might allow "tailoring" of immunosuppression, with increased therapy for those who need it most, and reduction in therapy and more rapid immune reconstitution in those who need it least. MacMillan found that a certain variation of the IL-2 gene increases the risk of acute GVHD, likely through increased IL-2 production.

Verfaillie's study on Parkinson's disease shows that cells from bone marrow of mice can be induced to differentiate into functioning dopaminergic neurons--the cells missing in patients with Parkinson's disease--outside the body. Studies to demonstrate that these cells can correct Parkinson's symptoms in the body are ongoing. "If that is the case," said Verfaillie, "marrow-derived pluripotent stem cells may be an ideal source of cells to treat this disease."

A second study by Verfaillie tested the effect of a gene known as BCR/ABL, responsible for causing chronic myelogenous leukemia (CML), on other genes expressed in hematopoietic (blood) stem cells. It was shown that a large number of genes were altered because of the presence of BCR/ABL. It was also shown that although some of these aberrations in gene expression were reversed by treating cells that have the BCR/ABL oncogene with the new anti-CML drug Gleevec, about 25-30 percent of genes are unaffected by the drug. "We believe that further characterization of these genes, not sensitive to Gleevec, may serve as new targets for novel therapies for CML," said Verfaillie.

Brenda Hudson, Academic Health Center, 612-624-5680

Deane Morrison, University News Service, 612-624-2346

University of Minnesota

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