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 CD8⁺ lymphocytes from donor bone marrow were studied in 29 patients undergoing transplantation from HLA-identical sibling (n = 20) or alternative (n = 9) donors. The direct immunomagnetic depletion method consistently removed > 95% of CD8⁺ cells and the non-specific loss of other cell subsets was only about 15%. Recovery of CFU-GM and BFU-e was on average >100%. The final graft contained 0.9 + 0.6 x 10⁸/kg nucleated cells and 1.4 ± 2.7 x 10⁵/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 regimen. One patient receiving an unrelated transplant failed to engraft. Median time to ANC > 500 x 10⁶/L was 17 (12-23) days. Four of 20 patients receiving grafts from HLA-identical siblings (20%) developed acute GVHD grade ≥ II. However, five of eight patients with grafts from alternative donors (63%) had grade ≥ II GVHD. Nearly all patients developed fever around day 7 accompanied by fluid overload, mild skin rash and shortness of breath. This syndrome necessitated treatment with steroids. Immunomagnetic CD8 depletion is a simple and reproducible method of selective T cell depletion. In combination with cyclosporine it appears to be effective in the prevention of severe acute GVHD in HLA-identical sibling transplants, but not in transplants from less perfectly matched donors.