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 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 regimen. One patient receiving an unrelated transplant failed to engraft. Median time to ANC > 500 x 10(6)/L was 17 (12-23) days. Four of 20 patients receiving grafts from HLA-identical siblings (20%) developed acute GVHD grade > or = II. However, five of eight patients with grafts from alternative donors (63%) had grade > or = 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.
Jansen
J
J
Bone Marrow Transplantation Program, Methodist Hospital of Indiana, Indianapolis 46206-1367, USA.
Hanks
S
S
Akard
L
L
Martin
M
M
Thompson
J
J
Chang
Q
Q
Ash
R
R
Garrett
P
P
Figg
F
F
English
D
D
D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D016827:CD8 Antigens / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D018189:Immunomagnetic Separation; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000473:pathology; D014184:Transplantation, Homologous / Q000276:immunology
D016827:CD8 Antigens