Specific depletion of alloreactive T cells in HLA-identical siblings: a method for separating graft-versus-host and graft-versus-leukaemia reactions

Abstract

Accumulating evidence indicates that alloreactive donor T cells confer both graft-versus-host (GVH) and graft-versus-leukaemia (GVL) reactivity following allogeneic bone marrow transplantation. We have developed a method to deplete alloreactive donor T cells with an immunotoxin targeting the alpha chain of the IL-2 receptor. In patients with chronic myeloid leukaemia and their HLA-identical sibling donors, we measured donor helper T-lymphocyte precursor frequencies (HTLPf) against recipient peripheral blood mononuclear cells (PBMNC; donor versus host), recipient leukaemia cells (donor versus leukaemia) and third-party PBMNC, 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 significant 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 1/155,000 before and 1/839,000 after depletion, P=0.007). There was a smaller non-significant 1.8-fold reduction in donor-versus-leukaemia HTLPf from 1/192,000 to 1/334,000 (P=0.19). These results suggest that selective T-cell depletion can significantly deplete donor anti-host reactivity while conserving anti-leukaemia reactivity in HLA-matched donor-recipient pairs.