SPECIFIC DEPLETION OF ALLOREACTIVE T-CELLS IN HLA-IDENTICAL SIBLINGS - A METHOD FOR SEPARATING GRAFT-VERSUS-HOST AND GRAFT-VERSUS-LEUKEMIA REACTIONS

Accumulating evidence indicates that alloreactive donor T cells confer both graft-versus-host (GVH) and graft-versus-leukaemia (GVL) reactiv ity following allogeneic bone marrow transplantation. We have develope d a method to deplete alloreactive donor T cells with an immunotoxin t argeting the alpha chain of the IL-2 receptor. In patients with chroni c myeloid leukaemia and their HLA-identical sibling donors, we measure d donor helper T-lymphocyte precursor frequencies (HTLPf) against reci pient peripheral blood mononuclear cells (PBMNC; donor versus host), r ecipient leukaemia cells (donor versus leukaemia) and third-party PBMN C, before and after the depletion. In seven pairs there was a 4.3-fold reduction of donor-versus-host HTLPf (P = 0.017), without a significa nt change in the donor frequencies against third party (P = 0.96). In eight further donor-recipient pairs, immunotoxin-depleted donor versus patient PBMNC HTLPf 4.5-fold (mean 1/1 5 5 000 before and 1/839 000 a fter depletion, P = 0.007). There was a smaller non-significant 1.8-fo ld reduction in donor-versus-leukaemia HTLPf from 1/192 000 to 1/334 0 00 (P = 0.19). These results suggest that selective T-cell depletion c an significantly deplete donor anti-host reactivity while conserving a ntileukaemia reactivity in HLA-matched donor-recipient pairs.