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

Instead of donor T cell depletion, we used CTLA4 and TJU103 (a small organi c compound believed to block CD4 binding to MHC II molecule of APC) to bloc k donor T lymphocyte activation in vitro before infusion, and mycophenolate mofetil to control the activity of lymphocytes of the recipient. We succes sfully treated a patient with an HLA-mismatched graft without donor T cell depletion. Mixed chimerism was observed 30 days and 60 days after transplan tation. STR-PCR showed that 28% and 62% of blood mononuclear cells (MNC) we re donor derived at day +30 and day +60, respectively, Mixed chimerism conv erted into full donor chimerism, when 99.7% of the MNC in the recipient wer e donor derived after three courses of DLI, A powerful GVL effect related t o mixed chimerism was observed. No acute GVHD occurred, only grade II chron ic GVHD occurred 6 months after transplant. Based on this case, we suggest that: (1) stable mixed chimerism can be intentionally established across HL A barriers without donor T cell depletion; (2) mixed chimerism can be conve rted into full donor chimerism by DLI; (3) mixed chimerism induced with thi s approach can be associated with a very powerful GVL effect, and these may be enhanced by DLI, without severe GVHD.