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 α 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 antileukaemia reactivity in HLA‐matched donor–recipient pairs.