SELECTIVE T-CELL DEPLETION WITH CD8-CONJUGATED MAGNETIC BEADS IN THE PREVENTION OF GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

The effects of a new immunomagnetic method of selectively depleting CD 8(+) lymphocytes from donor bone marrow were studied in 29 patients un dergoing transplantation from HLA-identical sibling (n=20) or alternat ive (n=9) donors, The direct immunomagnetic depletion method consisten tly removed >95% of CD8(+) cells and the non-specific loss of other ce ll subsets was only about 15%, Recovery of CFU-GM and BFU-e was on ave rage >100%, The final graft contained 0.9+/- 0.6 x 10(8)/kg nucleated cells and 1.4 +/- 2.7 x 10(5)/kg CD8(+) cells, Patients also received cyclosporine starting day -1, Engraftment occurred in 28 patients (97% ), including three patients who received a non-TBI conditioning regime n, One patient receiving an unrelated transplant failed to engraft, Me dian time to ANC >500 x 10(6)/L was 17 (12-23) days, Four of 20 patien ts receiving grafts from HLA-identical siblings (20%) developed acute GVHD grade greater than or equal to II. However, five of eight patient s with grafts from alternative donors (63%) had grade greater than or equal to II GVHD, Nearly all patients developed fever around day 7, ac companied by fluid overload, mild skin rash and shortness of breath, T his syndrome necessitated treatment with steroids, Immunomagnetic CD8 depletion is a simple and reproducible method of selective T cell depl etion, In combination with cyclosporine it appears to be effective in the prevention of severe acute GVHD in HLA-identical sibling transplan ts, but not in transplants from less perfectly matched donors.