title: 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.
authors.affiliation: Bone Marrow Transplantation Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20894, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Mavroudis
authors.forename: S
authors.initials: S
authors.lastname: Dermime
authors.forename: J
authors.initials: J
authors.lastname: Molldrem
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Jiang
authors.forename: A
authors.initials: A
authors.lastname: Raptis
authors.forename: F
authors.initials: F
authors.lastname: van Rhee
authors.forename: N
authors.initials: N
authors.lastname: Hensel
authors.forename: V
authors.initials: V
authors.lastname: Fellowes
authors.forename: G
authors.initials: G
authors.lastname: Eliopoulos
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D016026:Bone Marrow Transplantation / Q000379:methods*; D005434:Flow Cytometry / Q000379:methods; D006086:Graft vs Host Disease / Q000276:immunology*; D006087:Graft vs Host Reaction / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007118:Immunoassay / Q000379:methods; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy*; D008212:Lymphocyte Depletion / Q000379:methods*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014184:Transplantation, Homologous