| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
One major limitation of allogeneic bone marrow transplantation (BMT) is the lack of suitable donors. The results of transplantation with unrelated marrow grafts are, in general, inferior to those using matched sibling marrow, with an increased incidence and severity of graft-versus-host disease (GVHD), graft rejection and infections, although new immunosuppressive therapies have made the prophylaxis or treatment of GVHD more effective. Mobilized allogeneic peripheral blood cells (PBC) have recently been shown to be a potential source of stem cells for hematopoietic reconstitution after myeloablative therapy. Most importantly, more hematopoietic cells can be collected from blood than from bone marrow or cord/placenta. In a previous study, we demonstrated that negative depletion of T cells in unsatisfactory with PBC grafts, and is associated with a significant loss of hematopoietic progenitor cells. On the other hand, recently developed techniques for the positive selection/enrichment of CD34+ cells from marrow or PBC provide a convenient method for concentrating hematopoietic progenitors and depleting T cells. From this phase I clinical trial with 13 pediatric patients, we found that GVHD remained problematic after transplantation with enriched blood CD34+ cells, and no dose-dependent effect of T cells was seen for the induction of acute GVHD.The major infectious complication was cytomegalovirus infection, which was successfully managed with gamma-globulin and gancyclovir treatment with or without additional DLI.In conclusion, our results show that enriched blood CD34+ cells from a mismatched allogeneic donor can be a realistic alternative source of stem cells in patients who are at immediate risk of high-risk disease. The therapeutic efficacy and safety of periodic DLI as an integrated part of the protocol needs to be clarified in a further study.
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