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  • Title: Mixed chimera converted into full donor chimera with powerful graft-versus-leukemia effects but no graft-versus-host disease after non T cell-depleted HLA-mismatched peripheral blood stem cell transplantation.
    Author: Wu BY, Guo KY, Song CY, Yang, Li D.
    Journal: Bone Marrow Transplant; 2000 Sep; 26(6):691-3. PubMed ID: 11035376.
    Abstract:
    Instead of donor T cell depletion, we used CTLA4 and TJU103 (a small organic compound believed to block CD4 binding to MHC II molecule of APC) to block donor T lymphocyte activation in vitro before infusion, and mycophenolate mofetil to control the activity of lymphocytes of the recipient. We successfully treated a patient with an HLA-mismatched graft without donor T cell depletion. Mixed chimerism was observed 30 days and 60 days after transplantation. STR-PCR showed that 28% and 62% of blood mononuclear cells (MNC) were donor derived at day +30 and day +60, respectively. Mixed chimerism converted into full donor chimerism, when 99.7% of the MNC in the recipient were donor derived after three courses of DLI. A powerful GVL effect related to mixed chimerism was observed. No acute GVHD occurred, only grade II chronic GVHD occurred 6 months after transplant. Based on this case, we suggest that: (1) stable mixed chimerism can be intentionally established across HLA barriers without donor T cell depletion; (2) mixed chimerism can be converted into full donor chimerism by DLI; (3) mixed chimerism induced with this approach can be associated with a very powerful GVL effect, and these may be enhanced by DLI, without severe GVHD.
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