Experimental Study On Prevention Of GVHD By Selective Elimination Of Alloreactive Donor Lymphocytes Prior To Stem Cell Transplantation.

Objective To investigate a new concept aiming for induction of graft-vs-leukemia (GVL) effect prior to stem cell transplantation (SCT). Mismatched lymphocytes given pre-SCT will be followed by selective elimination of alloreactive donor lymphocytes, thus avoiding lethal graft-vs-host disease (GVHD).Methods Female (BALB/c×C57BL/6)F1 mice (H-2d/b) as recipients received sublethal total body irradiation (TBI) of 4 Gy (60Coγ-ray) on day 0 followed by being inoculated with P388D1 leukemia cell line on day 1,injection of allogeneic splenocytes supplied by C57BL/6 male mice(H-2b)for induction of GVHD, intraperitoneally injection of cyclophosphamide (CY) (200 mg/kg) or TBI (9 Gy) were given on day 7, one day later, treated mice were rescued with syngeneic bone marrow cells supplied by (BALB/c×C57BL/6)F1 male mice(H-2d/b).Results Recipients had no occurrence of leukemia and GVHD by selective elimination of alloreactive donor lymphocytes by CY and TBI,survived more than 210 days, to become complete-donor chimerism on day +21. The ratio of chimerism descended subsequently, but still displayed mixed-chimerism on day +90. Control mice died of evident GVHD,leukemia or other death-related-transplantation within 20 to 36 days(p<0.01).Conclusions Attempting to induce GVL effects by mismatched lymphocytes given before stem cell transplantation followed by selective elimination of alloreactive donor lymphocytes, thus avoiding graft-vs-host disease (GVHD) was feasible.