Specific depletion of alloreactive T cells in HLA-identical siblings: a method for separating graft-versus-host and graft-versus-leukaemia reactions.
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.
Mavroudis
D A
DA
Bone Marrow Transplantation Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20894, USA.
Dermime
S
S
Molldrem
J
J
Jiang
Y Z
YZ
Raptis
A
A
van Rhee
F
F
Hensel
N
N
Fellowes
V
V
Eliopoulos
G
G
Barrett
A J
AJ
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